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Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells 被引量:12
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作者 Xuchen Cao Bowen Liu +8 位作者 Wenfeng Cao Weiran Zhang Fei Zhang Hongmeng Zhao Ran Meng Lin Zhang Ruifang Niu Xishan Hao Bin Zhang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2013年第2期212-222,共11页
Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer ce... Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs) by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine (3-MA), significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control. 展开更多
关键词 apoptosis autophagy APIGENIN breast cancer 3-methyladenine
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Mechanisms of autophagy and apoptosis:Recent developments in breast cancer cells 被引量:1
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作者 Juan M Esteve Erwin Knecht 《World Journal of Biological Chemistry》 CAS 2011年第10期232-238,共7页
Autophagy,the pathway whereby cell components are degraded by lysosomes,is involved in the cell response to environmental stresses,such as nutrient deprivation,hypoxia or exposition to chemotherapeutic agents.Under th... Autophagy,the pathway whereby cell components are degraded by lysosomes,is involved in the cell response to environmental stresses,such as nutrient deprivation,hypoxia or exposition to chemotherapeutic agents.Under these conditions,which are reminiscent of certain phases of tumor development,autophagy either promotes cell survival or induces cell death. This strengthens the possibility that autophagy could be an important target in cancer therapy,as has been proposed.Here,we describe the regulation of survival and death by autophagy and apoptosis,especially in cultured breast cancer cells.In particular,we discuss whether autophagy represents an apoptosis-independent process and/or if they share common pathways. We believe that understanding in detail the molecular mechanisms that underlie the relationships between autophagy and apoptosis in breast cancer cells could improve the available treatments for this disease. 展开更多
关键词 autophagy apoptosis SURVIVAL breast cancer cells Signaling PATHWAYS
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Discovery of a novel eEF2K inhibitor (BL-EKI03) that induces ER stress, autophagy and apoptosis in breast cancer
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期231-232,共2页
Aim Recent evidence has revealed that Eukaryotic elongation factor-2 kinase (eEF2K) activity may confer cancer cell adaptation to metabolic stress, and high expression of eEF2K is found in several types of cancer. T... Aim Recent evidence has revealed that Eukaryotic elongation factor-2 kinase (eEF2K) activity may confer cancer cell adaptation to metabolic stress, and high expression of eEF2K is found in several types of cancer. Therefore, eEF2K may contribute to carcinogenesis and represent a promising therapeutic target; however, inhibi- tion of eEF2K for cancer drug discovery still remains in its infancy. This study aimed at developing a series of eEF2K inhibitor as candidate anti-tumor drugs in breast cancer and illustrating the possible mechanisms of its anti- tumor activity in vitro and in vivo. Methods In silico screening, structure modifications, MTT assay and molecular dynamics (MD) simulations were applied for the discovery of the novel eEF2K inhibitor (BL-EKI03). Observa- tions of cell morphology were executed through several methods including ER-traeker, MDC and Hoeehst 33258 staining and GFP-LC3 transfeetion. Flow eytometrie analyses of MDC and Annexin V/PI were used for quantifica- tion of autophagy and apoptosis ratio. Western blot and ITRAQ analysis were used to explore the detailed mecha- nisms of BL-EKI03-induced ER stress, autophagie death and apoptosis in breast cancer cells. Furthermore, an in vivo xenograft mouse model was established for validating the anti-tumor efficacy of BL-EKI03. Results Firstly, a novel eEF2K inhibitor (BL-EKI03) with a good affinity for eEF2K was eventually discovered after computational screening and synthesis of a series of candidate compounds targeting eEF2K. Subsequently, our results demonstra- ted that BL-EKI03 has remarkable anti-proliferative activities and induces endoplasmie retieulum (ER) stress, au- tophagy and apoptosis in MCF-7 and MDA-MB-436 cells. More importantly, the mechanism for BL-EKI03-indueed autophagie death involves eEF2K-mediated AMPK-mTOR-ULK complex pathways. The proteomies analyses and ex-perimental validation revealed that the BL-EKI03-induced mechanism was also involved BIRC6, BNIP1, SNAP29 and Bif-1, which might be regulated by eEF2K. Moreover, BL-EKI03 exerted its anti-tumor activities without re- markable toxicity, and it also induced autophagy and apoptosis by targeting eEF2K in fifo. Conclusion In this study, a novel eEF2K inhibitor (BL-EKI03) was discovered with remarkable anti-proliferative activities and in- duced endoplasmic reticulum (ER) stress, autophagy and apoptosis of breast cancer in vitro and in fifo. These findings highlight a new small-molecule eEF2K inhibitor (BL-EKI03) that has the potential to impact future breast cancer therapy. 展开更多
关键词 EUKARYOTIC elongation factor-2 kinase (eEF2K)lure (ER) stress autophagy apoptosis breast cancer. eEF2K INHIBITOR (BL-EKI03) endoplasmic reticu-
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Apogossypolone, a novel inhibitor of anfiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro 被引量:10
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作者 Xian-Qing Zhang Xiao-Feng Huang +8 位作者 Xing-Bin Hu Yong-Hua Zhan Qun-Xing An Shi-Ming Yang Ai-Jun Xia Jing Yi Rui Chen Shi-Jie Mu Dao-Cheng Wu 《Asian Journal of Andrology》 SCIE CAS CSCD 2010年第5期697-708,共12页
Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkyl... Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone (ApoG2) and (-)-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-Ⅱ and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells. 展开更多
关键词 apogossypolone apoptosis autophagy prostate cancer
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MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy 被引量:14
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期243-243,共1页
Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER + ) breast cancers. Howev... Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER + ) breast cancers. Howev- er, the development of endocrine resistance is the impediment for successful treatment. In this study, we explored the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Methods The experiments were performed in Ell + and estrogen/TAM-sensitive MCF7 cells and antiestrogen-re- sistant MCF7/LCC9 cells. Western blot and confocal microscopy were used to determine cell autophagy. Cell trans- fection and luciferase activity assay were performed to identify the target gene of miR-214. Results It showed that 4-OHT/FUL treatment induced apoptosis as well as autophagy in breast cancer cells. The increase of autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. Mill-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correla- tion was established between miR-214 and UCP2 in human breast cancer tissue specimens by RT-qPCR assay. UCP2 was identified to be a direct target of mill-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3 K-Akt-mTOll pathway, thereby inducing autophagy by overexpres- sion of UCP2. Conclusions MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through in- hibition of autophagy by targeting UCP2. Mill-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER + breast cancers. 展开更多
关键词 ER + breast cancer ENDOCRINE resistance apoptosis autophagy miR-214 UCP2
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Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer 被引量:1
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作者 Michelle Bowie Patrick Pilie +9 位作者 Julia Wulfkuhle Siya Lem Abigail Hoffman Shraddha Desai Emanuel Petricoin Amira Carter Adrian Ambrose Victoria Seewaldt Dihua Yu Catherine Ibarra Drendall 《World Journal of Clinical Oncology》 CAS 2015年第6期299-311,共13页
AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in t... AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine(FLX) in representative molecular subtypes of breast cancer.METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative(SUM149PT) and luminal(T47D and Au565) cancer cells and nontransformed MCF10 A were investigated. Reverse phase protein microarray(RPPM) was performed with and without 10 μmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10 A. In comparison to the other lines,cell growth reduction in SUM149 PT coincided with significant induction of endoplasmic reticulum(ER) stress and autophagy after 24 and 48 h of 10 μmol/L FLX,resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker,cleaved microtubule-associated protein 1 light chain 3,in SUM149 PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently,the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis,growth arrest at the G1 phase,autophagy,and caspase-7-mediated cell death.CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy,resulting in death of aggressive triple negative breast cancer SUM149 PT. 展开更多
关键词 INFLAMMATORY breast cancer Endoplasmic reticulum stress autophagy apoptosis FLUOXETINE
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Hexadecanoic acid-enriched extract of Halymenia durvillei induces apoptotic and autophagic death of human triple-negative breast cancer cells by upregulating ER stress 被引量:4
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作者 Kant Sangpairoj Rapeewan Settacomkul +6 位作者 Tanapan Siangcham Krai Meemon Nakorn Niamnont Nilubon Sornkaew Montakan Tamtin Prasert Sobhon Pornpun Vivithanaporn 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2022年第3期132-140,共9页
Objective:To investigate the effect of the hexane solvent fraction of Halymenia durvillei(HDHE)on triple-negative breast cancer.Methods:The phytochemical profile of HDHE was investigated by GC-MS.The cytotoxicity of H... Objective:To investigate the effect of the hexane solvent fraction of Halymenia durvillei(HDHE)on triple-negative breast cancer.Methods:The phytochemical profile of HDHE was investigated by GC-MS.The cytotoxicity of HDHE against MDA-MB-231 cells was determined.The apoptotic and autophagic effects of HDHE were analyzed.The expression of molecular markers controlling apoptosis,autophagy,DNA damage,and endoplasmic reticulum(ER)stress was determined.Results:HDHE contains a mixture of fatty acids,mainly hexadecanoic acid.HDHE at a cytotoxic concentration induced apoptotic death of MDA-MB-231 cells through mitochondrial membrane dysfunction,and induction of apoptosis markers,and increased the expression of proteins related to DNA damage response.HDHE also induced the expression of LC-3,a marker of autophagic cell death at a cytotoxic concentration.Moreover,HDHE modulated the expression of ER stress genes.Conclusions:The hexadecanoic acid-enriched extract of Halymenia durvillei promotes apoptosis and autophagy of human triple-negative breast cancer cells.This extract may be further explored as an anticancer agent for triple-negative breast cancer. 展开更多
关键词 Halymenia durvillei Triple-negative breast cancer apoptosis autophagy Endoplasmic reticulum stress Red algae Hexadecanoic acid
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Apogossypolone诱导前列腺癌PC-3细胞在体外的自噬 被引量:1
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作者 袁青 陈晓鹏 +4 位作者 黄晓峰 穆士杰 胡兴斌 尹文 张献清 《肿瘤防治研究》 CAS CSCD 北大核心 2011年第9期1006-1011,共6页
目的研究ApoG2对前列腺癌PC-3细胞在体外的作用,了解其杀伤肿瘤细胞的机制。方法采用MTT法、吖啶橙染色、透射电镜、流式细胞技术、Western blot、免疫组织化学等方法观察了ApoG2对PC-3细胞的自噬与凋亡的诱导作用。结果 ApoG2可明显抑... 目的研究ApoG2对前列腺癌PC-3细胞在体外的作用,了解其杀伤肿瘤细胞的机制。方法采用MTT法、吖啶橙染色、透射电镜、流式细胞技术、Western blot、免疫组织化学等方法观察了ApoG2对PC-3细胞的自噬与凋亡的诱导作用。结果 ApoG2可明显抑制PC-3细胞增殖;ApoG2作用于PC-3细胞72小时可诱导细胞自噬;加入自噬抑制剂3-MA可增强ApoG2诱导凋亡作用;ApoG2可以增强细胞内LC-3Ⅱ及Beclin-Ⅰ的表达,降低Bcl-2的表达水平。结论 ApoG2主要以诱导PC-3细胞发生自噬为主,抑制自噬可以促进凋亡的发生。 展开更多
关键词 ApoG2 人前列腺癌PC-3细胞 自噬 凋亡
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Augmented efficacy and the mechanism of a combined use of daunorubicin with rofecoxib in treatment of triple-negative breast cancer
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作者 赵曜 张婧莹 +3 位作者 胡英杰 吴佳栓 卜英子 吕万良 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2016年第6期438-447,共10页
Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor-2(HER2). A regular chemotherapy cannot eradicate t... Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor-2(HER2). A regular chemotherapy cannot eradicate triple-negative breast cancer. In the present study, we aimed to develop a combined use of daunorubicin and rofecoxib to treat triple-negative breast cancer, and reveal the underlying mechanisms. A gradient elution HPLC-UV method was developed for quantification, and the evaluations were performed on the triple-negative breast cancer MDA-MB-231 cells using a high content screening system. The results demonstrated that daunorubicin alone was insensitive to the triple negative breast cancer cells, while the combined use of daunorubicin and rofecoxib was able to effectively kill these triple-negative cancer cells, exhibiting a rofecoxib concentration-dependent manner. The mechanism revealed that the augmented anticancer efficacy was associated with direct killing effect, inducing apoptosis and inducing autophagy by the combination treatment. Besides, the apoptosis signaling pathways were correlated to a cascade of reactions by activating apoptotic enzyme caspase family and by suppressing anti-apoptotic gene expressed protein Bcl-2 family. In conclusion, this study provided a fundamental evidence for further developing the combined use of daunorubicin and rofecoxib formulation, hence offering a promising strategy for eradicating the triple negative breast cancer. 展开更多
关键词 DAUNORUBICIN ROFECOXIB Triple-negative breast cancer apoptosis autophagy
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Mfn2过表达诱导乳腺癌细胞线粒体自噬促进细胞凋亡的机制研究
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作者 茅芯慧 张建庆 +1 位作者 王珍 朱成斌 《现代肿瘤医学》 CAS 2024年第19期3670-3676,共7页
目的:探究线粒体融合基因2(Mfn2)过表达诱导乳腺癌细胞凋亡的作用及机理。方法:收集乳腺癌患者肿瘤组织及癌旁组织标本,通过实时荧光定量聚合酶链式反应(qRT-PCR)、蛋白质免疫印迹(Western Blot)及免疫组织化学染色检测两种组织中Mfn2... 目的:探究线粒体融合基因2(Mfn2)过表达诱导乳腺癌细胞凋亡的作用及机理。方法:收集乳腺癌患者肿瘤组织及癌旁组织标本,通过实时荧光定量聚合酶链式反应(qRT-PCR)、蛋白质免疫印迹(Western Blot)及免疫组织化学染色检测两种组织中Mfn2表达差异。将MCF-7细胞分为对照组、NC组、Mfn2组、Mfn2+3-MA组,按照分组进行对应处理后,收集4组细胞,CCK-8法测定细胞增殖活性,流式细胞术检测细胞凋亡率,DCFH-DA探针检测细胞内活性氧(ROS)水平,JC-1染色检测线粒体膜电位,Western Blot检测细胞中PTEN诱导激酶1(PINK1)、E3泛素连接酶(Parkin)、微管相关蛋白1轻链3(LC3)Ⅱ/LC3Ⅰ、p62蛋白表达。结果:与癌旁组织比较,乳腺癌组织中Mfn2 mRNA相对表达量和蛋白相对表达量显著下调(P<0.05),阳性细胞比例显著减少(P<0.05)。转染Mfn2重组过表达质粒的MCF-7细胞中Mfn2 mRNA相对表达量和蛋白相对表达量显著高于未转染的MCF-7细胞、转染阴性对照NC重组质粒的MCF-7细胞(P<0.05)。与对照组比较,Mfn2组MCF-7细胞增殖活性显著降低(P<0.05),细胞凋亡率显著增加(P<0.05),细胞内ROS水平显著升高(P<0.05),线粒体膜电位显著下降(P<0.05),细胞中PINK1、Parkin、LC3Ⅱ/LC3Ⅰ蛋白表达水平均显著上调(P<0.05),p62蛋白表达水平显著下调(P<0.05);与Mfn2组比较,Mfn2+3-MA组MCF-7细胞增殖活性显著升高(P<0.05),细胞凋亡率显著减少(P<0.05),细胞内ROS水平显著降低(P<0.05),线粒体膜电位显著升高(P<0.05),细胞中PINK1、Parkin、LC3Ⅱ/LC3Ⅰ蛋白表达水平均显著下调且p62蛋白表达水平显著上调(P<0.05)。结论:乳腺癌组织中Mfn2低表达,在乳腺癌细胞中过表达Mfn2能够通过诱导线粒体自噬促进细胞凋亡,起到肿瘤抑制作用。 展开更多
关键词 乳腺癌 线粒体融合基因2 线粒体 自噬 细胞凋亡
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白藜芦醇抗乳腺癌的研究进展
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作者 高庆东 段旭昉 +3 位作者 李妍 许涛 于洋洋 白国栋 《中国药房》 CAS 北大核心 2024年第11期1408-1412,共5页
乳腺癌的发病率在女性恶性肿瘤中高居榜首,具有侵袭性强、恶性程度高、预后差的特征。白藜芦醇是一种植物抗氧化剂,在对抗乳腺癌发生和发展中具有潜在的多效性。本文通过评估多个体外和体内研究以探索白藜芦醇干预乳腺癌的作用机制,发... 乳腺癌的发病率在女性恶性肿瘤中高居榜首,具有侵袭性强、恶性程度高、预后差的特征。白藜芦醇是一种植物抗氧化剂,在对抗乳腺癌发生和发展中具有潜在的多效性。本文通过评估多个体外和体内研究以探索白藜芦醇干预乳腺癌的作用机制,发现白藜芦醇可通过诱导细胞凋亡,调控自噬,抑制糖酵解,调节肿瘤微环境、基质金属蛋白酶、上皮-间质转化、耐药蛋白等的表达,来削弱乳腺癌细胞的增殖和存活能力,抑制乳腺癌细胞的生长、转移和侵袭,逆转乳腺癌细胞对阿霉素的耐药。白藜芦醇的临床试验研究数量有限,主要是关于其对乳腺癌的预防作用,这可能是影响全面评估白藜芦醇抗癌效果的原因之一。 展开更多
关键词 白藜芦醇 乳腺癌 细胞凋亡 自噬 糖酵解 肿瘤微环境 细胞侵袭 细胞转移 耐药
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羟基积雪草酸对乳腺癌MCF-7细胞增殖、凋亡和自噬的影响
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作者 谢珠珠 杨柯鸿 +3 位作者 冯文静 邹攀 钱荣康 钱荣华 《湖南中医药大学学报》 CAS 2024年第5期771-777,共7页
目的探讨羟基积雪草酸(madecassic acid,MA)对乳腺癌MCF-7细胞增殖、凋亡及自噬的影响。方法将MCF-7细胞分为阴性对照组、不同浓度的MA(80、100、120、140、160μmol/L)组、不同浓度的他莫昔芬(10、20、30、40、50、35μmol/L)组,干预24... 目的探讨羟基积雪草酸(madecassic acid,MA)对乳腺癌MCF-7细胞增殖、凋亡及自噬的影响。方法将MCF-7细胞分为阴性对照组、不同浓度的MA(80、100、120、140、160μmol/L)组、不同浓度的他莫昔芬(10、20、30、40、50、35μmol/L)组,干预24、36、48 h。初步确定MA发挥抗乳腺癌作用的最佳浓度和最佳时间后,采用MTT法检测细胞活力,计算相应的半抑制浓度(half maximal inhibitory concentration,IC50)值;流式细胞术检测细胞凋亡;JC-1荧光探针检测线粒体膜电位变化;Western blot法检测细胞增殖蛋白细胞核抗原蛋白(proliferating cell nuclear antigen,PCNA)、自噬蛋白苄氯素-1(Beclin-1)、微管相关蛋白1轻链3-Ⅱ/Ⅰ(microtubule-associated protein1 light chain 3Ⅱ/Ι,LC3Ⅱ/Ι)、螯合体1(protein 62,p62)的蛋白相对表达水平。透射电镜检测自噬小体。结果发挥抗肿瘤作用的他莫昔芬最佳浓度为35μmol/L,MA最佳浓度为140μmol/L,最佳时间均为48 h。与阴性对照组相比,MA140μmol/L组和他莫昔芬35μmol/L组的细胞凋亡率,细胞荧光相对强度以及LC3Ⅱ/Ⅰ、Beclin-1蛋白相对表达水平均升高(P<0.05,P<0.01);PCNA、P62蛋白相对表达水平降低(P<0.05,P<0.01)。与MA 140μmol/L组相比,他莫昔芬35μmol/L组细胞凋亡率、细胞荧光相对强度以及Beclin-1蛋白相对表达水平明显升高(P<0.01),PCNA蛋白相对表达水平明显降低(P<0.01)。阴性对照组MCF-7细胞膜完整,核膜清晰,细胞形态良好;MA 140μmol/L组细胞膜、细胞核形态不规则,线粒体基质密度较高、嵴扩张,可见自噬小体;他莫昔芬35μmol/L组细胞膜局部溶解、破损,可见双核仁,线粒体肿胀、基质溶解,可见自噬小体。结论MA可抑制乳腺癌MCF-7细胞的增殖、诱导细胞凋亡和自噬。 展开更多
关键词 乳腺癌 羟基积雪草酸 增殖 凋亡 自噬 MCF-7细胞
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基于自噬抑制剂3-MA介导的大叶蛇葡萄总黄酮提取物对人乳腺癌细胞增殖、凋亡的影响
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作者 许诗怡 廖思雨 +3 位作者 张天旭 邹雪 桂春 张秀桥 《中国药理学通报》 CAS CSCD 北大核心 2024年第6期1115-1123,共9页
目的探讨抑制自噬时,大叶蛇葡萄总黄酮提取物(total flavonoid extract,TFE)对人乳腺癌细胞增殖、凋亡的影响及其作用机制。方法针对人宫颈癌细胞Hela、人肺癌细胞A549、人肝癌细胞SMMC-7721、人乳腺癌细胞MCF-7、MDA-MB-231及人正常肝... 目的探讨抑制自噬时,大叶蛇葡萄总黄酮提取物(total flavonoid extract,TFE)对人乳腺癌细胞增殖、凋亡的影响及其作用机制。方法针对人宫颈癌细胞Hela、人肺癌细胞A549、人肝癌细胞SMMC-7721、人乳腺癌细胞MCF-7、MDA-MB-231及人正常肝细胞L-02,采用MTT法优选敏感细胞株;通过TFE与自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)联合运用,采用MTT法检测其对敏感细胞增殖的抑制作用;透射电子显微镜及Hoechst 33258单染法观察细胞的形态学变化;Annexin V-FITC/PI双染法检测细胞凋亡率的变化;Western blot检测凋亡相关蛋白和通路蛋白(死亡受体途径、线粒体途径、内质网应激途径)的表达水平;免疫荧光法检测线粒体途径关键蛋白Cyt-c表达,并选择自噬激动剂雷帕霉素(rapamycin,RA)进行反向验证。结果TFE可浓度依赖性抑制人乳腺癌细胞增殖,MCF-7细胞为敏感细胞株,与TFE组相比,TFE+3-MA组在24、48、72 h对MCF-7细胞的抑制率均明显增加(P<0.01),细胞数量减少、间隙增大,凋亡小体增多,凋亡率升高(P<0.01),Bax/Bcl-2(P<0.01)、cleaved caspase-3(P<0.01)、Cyt-c(P<0.05)、FADD、cleaved caspase-12的表达量均升高,核内凋亡蛋白Cyt-c表达增加;TFE+RA组荧光减弱,逆转了TFE诱导的线粒体途径凋亡。结论TFE能明显抑制人乳腺癌细胞的增殖,抑制自噬时可能通过线粒体途径促进MCF-7细胞凋亡,激活自噬可逆转细胞凋亡。 展开更多
关键词 大叶蛇葡萄总黄酮提取物 抑制自噬 乳腺癌细胞 MCF-7细胞 增殖 凋亡
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银杏内酯K调节AMPK/mTOR/ULK1信号通路对乳腺癌细胞自噬和凋亡的影响
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作者 时延龙 周鹏 +1 位作者 王雪凯 郭煜 《西部医学》 2024年第1期42-46,共5页
目的 探讨银杏内酯K(GK)调节AMPK/mTOR/ULK1信号通路对乳腺癌细胞自噬和凋亡的影响。方法 取对数生长期的MCF-7细胞,设置分组为对照组、GK低浓度(GK-L,12.5μg/mL)组、GK中浓度(GK-M,25μg/mL)组、GK高浓度(GK-H,50μg/mL)组、GK-H+AMP... 目的 探讨银杏内酯K(GK)调节AMPK/mTOR/ULK1信号通路对乳腺癌细胞自噬和凋亡的影响。方法 取对数生长期的MCF-7细胞,设置分组为对照组、GK低浓度(GK-L,12.5μg/mL)组、GK中浓度(GK-M,25μg/mL)组、GK高浓度(GK-H,50μg/mL)组、GK-H+AMPK抑制剂(Compound C,50μg/mL GK+50μmol/L Compound C)组。观察各组细胞形态以及细胞增殖、凋亡、自噬状况并分析自噬相关基因LC3、P62、Beclin1 mRNA表达以及AMPK、p-mTOR、mTOR、p-ULK1、ULK1、LC3、P62、Beclin1表达。结果 与对照组相比,GK-L、GK-M、GK-H组细胞自噬泡数量增多,增殖率、p-mTOR/mTOR、p-ULK1/ULK1、p62表达显著下降,凋亡率、LC3、Beclin1表达、AMPK蛋白表达显著增加(P<0.05);与GK-H组相比,GK-H+Compound C组细胞自噬泡数量减少,增殖率、p-mTOR/mTOR、p-ULK1/ULK1、p62显著增加,凋亡率、LC3、Beclin1表达、AMPK蛋白表达显著降低(P<0.05)。结论 GK可以诱导乳腺癌细胞自噬和凋亡、抑制其增殖,可能与激活AMPK/mTOR/ULK1信号通路有关。 展开更多
关键词 银杏内酯K 乳腺癌细胞 自噬 凋亡 AMPK/mTOR/ULK1
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苦参碱对人乳腺癌MCF-7细胞自噬及细胞凋亡的影响 被引量:5
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作者 贾绍华 孙萌遥 +1 位作者 丁海鑫 金诗鹏 《中药材》 CAS 北大核心 2023年第3期724-729,共6页
目的:研究苦参碱对人乳腺癌MCF-7细胞自噬及凋亡的影响,并分析其机制,探索二者之间潜在的关系。方法:采用MTT法和Annexin V/PI双染法检测细胞增殖活力和凋亡率;自噬双标腺病毒法(mRFP-GFP-LC3)和透射电镜法检测细胞自噬水平;Western Blo... 目的:研究苦参碱对人乳腺癌MCF-7细胞自噬及凋亡的影响,并分析其机制,探索二者之间潜在的关系。方法:采用MTT法和Annexin V/PI双染法检测细胞增殖活力和凋亡率;自噬双标腺病毒法(mRFP-GFP-LC3)和透射电镜法检测细胞自噬水平;Western Blot检测自噬相关蛋白Beclin-1、LC3及凋亡相关蛋白Caspase-3、cleaved-Caspase-3、cleaved-Caspase-9的表达;运用自噬抑制剂(3-MA)和凋亡抑制剂(Z-VAD-FMK)对上述相关指标进行干预。结果:苦参碱在未加入抑制剂干预的情况下可显著抑制MCF-7细胞的增殖,提高凋亡率和自噬水平,可上调自噬相关蛋白Beclin-1、LC3和凋亡相关蛋白cleaved-Caspase-3、cleaved-Caspase9的表达(P<0.05或P<0.01)。加入自噬抑制剂(3-MA)后,细胞存活率显著降低,凋亡率显著升高(P<0.05);加入凋亡抑制剂(Z-VAD-FMK)后,自噬水平显著升高(P<0.05)。结论:苦参碱可诱导人乳腺癌MCF-7细胞凋亡和细胞自噬,二者之间可能存在着互相调控的关系。 展开更多
关键词 苦参碱 人乳腺癌MCF-7细胞 细胞凋亡 细胞自噬 相关性
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去甲斑蝥素通过诱导自噬体聚集促使乳腺癌MDA-MB-231细胞凋亡 被引量:1
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作者 夏源 姜庆玲 +3 位作者 王晓婷 李敏敬 郑秋生 李德芳 《中国药科大学学报》 CAS CSCD 北大核心 2023年第6期757-768,共12页
探究去甲斑蝥素(norcantharidin,NCTD)对三阴性乳腺癌MDA-MB-231细胞增殖和凋亡的影响。采用Western blot实验检测NCTD对MDA-MB-231细胞中凋亡相关蛋白Bax/Bcl-2、cleaved-PARP/PARP、cleaved-caspase-9、cleaved-caspase-3和MCL-1表达... 探究去甲斑蝥素(norcantharidin,NCTD)对三阴性乳腺癌MDA-MB-231细胞增殖和凋亡的影响。采用Western blot实验检测NCTD对MDA-MB-231细胞中凋亡相关蛋白Bax/Bcl-2、cleaved-PARP/PARP、cleaved-caspase-9、cleaved-caspase-3和MCL-1表达水平的影响;采用Western blot实验检测NCTD对MDA-MB-231细胞中自噬相关蛋白LC3-II/LC3-I,Parkin和PINK1表达水平的影响;采用流式细胞术检测NCTD对MDA-MB-231细胞线粒体膜电位及线粒体活性氧(reactive oxygen species,ROS)变化情况的影响;采用共聚焦显微镜检测NCTD对表达mCherry-EGFP-LC3的MDA-MB-231细胞自噬流的影响;采用流式细胞术检测NCTD联合使用氯喹(chloroquine,CQ)或3-甲基腺嘌呤(3-methyladenine,3-MA)后,对MDA-MB-231细胞凋亡情况的影响。实验结果显示,NCTD可显著上调Bax/Bcl-2、cleaved-PARP/PARP、cleaved-caspase-9、cleavedcaspase-3以及LC3-II/LC3-I蛋白的表达水平,促进Parkin的线粒体易位,阻断自噬流。此外,NCTD联合使用CQ加剧了细胞凋亡,而NCTD联合使用3-MA则减少了细胞凋亡。研究结果表明,NCTD可以诱导自噬体积累并导致MDA-MB-231细胞凋亡。 展开更多
关键词 乳腺癌 MDA-MB-231细胞 去甲斑蝥素 凋亡 自噬
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TRAIL联合顺铂诱导三阴乳腺癌MDA-MB-231细胞过度性自噬的分子机制 被引量:1
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作者 岳子雯 杨彪 +1 位作者 刘皓 周伟强 《中国药理学通报》 CAS CSCD 北大核心 2023年第8期1599-1600,共2页
流行病学报道,乳腺癌成为目前女性发病率和死亡率最高的癌症[1]。而铂类药物也是临床上最常用的周期非特异性抗肿瘤药物,在临床治疗实体肿瘤中显示了良好的疗效[2]。其中顺铂作为一线临床的传统用药,其靶点选择范围窄、疗效差、易耐药... 流行病学报道,乳腺癌成为目前女性发病率和死亡率最高的癌症[1]。而铂类药物也是临床上最常用的周期非特异性抗肿瘤药物,在临床治疗实体肿瘤中显示了良好的疗效[2]。其中顺铂作为一线临床的传统用药,其靶点选择范围窄、疗效差、易耐药等问题,尚未得到解决。肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)属于肿瘤坏死因子(tumor necrosis factor,TNF)超家族。 展开更多
关键词 顺铂 肿瘤坏死因子相关凋亡诱导配体 三阴乳腺癌 自噬 MDA-MB-231 细胞凋亡
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miR-101对乳腺癌患者的诊断及对乳腺癌细胞自噬和凋亡的影响
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作者 宋雅琪 张志生 +1 位作者 孔令霞 刘进宇 《河北医学》 CAS 2023年第8期1240-1245,共6页
目的:探讨血清miR-101在乳腺癌患者中的表达和临床特征,以及对MCF-7细胞自噬和凋亡的影响。方法:选择2021年6月至2022年10月收治的96名乳腺癌患者作为观察组,41例乳腺良性增生患者作为良性组,35名健康体检者作为正常对照组。qRT-PCR检测... 目的:探讨血清miR-101在乳腺癌患者中的表达和临床特征,以及对MCF-7细胞自噬和凋亡的影响。方法:选择2021年6月至2022年10月收治的96名乳腺癌患者作为观察组,41例乳腺良性增生患者作为良性组,35名健康体检者作为正常对照组。qRT-PCR检测3组血清miR-101的表达水平;比较乳腺癌患者不同临床病理特征血清miRNA-101表达水平;ROC曲线分析miR-101的诊断价值。应用miR-101 mimic试剂对乳腺癌细胞株(MCF-7)进行转染,qPCR法检测MCF-7和正常乳腺细胞株(HBL-100)miR-101的表达;CCK-8法检测各组细胞的增殖;qPCR法和Western blot法检测细胞自噬和凋亡基因和蛋白的表达;流式细胞术检测各组凋亡率。结果:观察组miRNA-145相对表达量(n=96,0.27)显著低于良性组(n=41,0.63)和对照组(n=35,1.00),差异有统计学意义(P<0.01)。血清miRNA-101的表达在淋巴结转移、分化程度、肿瘤直径和TNM分期差异具有显著性(P<0.01)。ROC曲线分析显示,在3组对比中,曲线下面积分别为0.723(95%CI:0.813-0.924)和0.875(95%CI:0.835~0.981)。CCK-8、qPCR和Western blot结果显示,miR-101过表达可抑制MCF-7细胞增殖,显著增加MCF-7细胞BAX的基因和蛋白表达(P<0.01),降低BCL-2、LC3B和Beclin-1基因和蛋白的表达(P<0.01),增加MCF-7细胞凋亡率。结论:在乳腺癌患者中,血清miR-101的表达水平显著降低,可能成为潜在的乳腺癌的诊断指标。此外,miR-101过表达具有抑制MCF-7乳腺癌细胞增殖、抑制自噬,并促进细胞凋亡的作用。这些结果为进一步研究miR-101在乳腺癌发生和发展中的机制提供了重要线索,为乳腺癌的早期诊断和治疗提供了新的策略。 展开更多
关键词 乳腺癌 自噬 凋亡
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紫草素诱导人乳腺癌MCF-7细胞自噬对细胞增殖及凋亡的影响
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作者 苗久旺 高荧 于宜平 《临床医学研究与实践》 2023年第6期5-8,共4页
目的探讨紫草素诱导人乳腺癌MCF-7细胞自噬对细胞增殖及凋亡的影响。方法以2.5、5、10、20μmol/L紫草素单用或与2 mmol/L自噬抑制剂3-甲基腺嘌呤(3-MA)联用干预MCF-7细胞24 h或48 h。采用四甲基偶氮唑盐(MTT)比色法检测细胞增殖;采用5... 目的探讨紫草素诱导人乳腺癌MCF-7细胞自噬对细胞增殖及凋亡的影响。方法以2.5、5、10、20μmol/L紫草素单用或与2 mmol/L自噬抑制剂3-甲基腺嘌呤(3-MA)联用干预MCF-7细胞24 h或48 h。采用四甲基偶氮唑盐(MTT)比色法检测细胞增殖;采用5μmol/L紫草素单用或与2 mmol/L 3-MA联用干预MCF-7细胞48 h,以Annexin V-FITC/PI双染法检测细胞凋亡率;采用Western blot方法检测MCF-7细胞LC3B和活化型半胱氨酸蛋白酶-3(cleaved-caspase 3)的活性表达。结果2.5、5、10、20μmol/L紫草素+2 mmol/L 3-MA组的细胞抑制率均明显高于紫草素单用组,差异具有统计学意义(P<0.05)。5μmol/L紫草素+2 mmol/L 3-MA组的细胞凋亡率明显高于5μmol/L紫草素组,差异具有统计学意义(P<0.05)。5μmol/L紫草素+2 mmol/L 3-MA组的LC3BⅡ/LC3BⅠ相对比值明显低于5μmol/L紫草素组(P<0.05);5μmol/L紫草素+2 mmol/L 3-MA组的cleaved-caspase 3相对值明显高于5μmol/L紫草素组(P<0.01)。结论紫草素诱导MCF-7细胞发生自噬后,可能对细胞增殖有促进作用,并抑制细胞凋亡。 展开更多
关键词 紫草素 乳腺癌 细胞自噬 细胞增殖 细胞凋亡
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MiR-148 b-3 p/FOXO 4轴对乳腺癌细胞自噬及生长的影响
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作者 郭玲 陈敬信 《临床与病理杂志》 CAS 2023年第9期1621-1630,共10页
目的:MiR-148b-3p通过调节叉头框蛋白O4(forkhead box O4,FOXO4)在乳腺癌(breast cancer,BC)进展中的作用还未完全阐明。本研究探究miR-148b-3p调节FOXO4表达对BC细胞增殖、凋亡和自噬的影响。方法:采用实时反转录聚合酶链反应(real-tim... 目的:MiR-148b-3p通过调节叉头框蛋白O4(forkhead box O4,FOXO4)在乳腺癌(breast cancer,BC)进展中的作用还未完全阐明。本研究探究miR-148b-3p调节FOXO4表达对BC细胞增殖、凋亡和自噬的影响。方法:采用实时反转录聚合酶链反应(real-time reverse transcription polymerase chain reaction,real-time RT-PCR)检测BC患者的癌组织标本(BC组织)和邻近的非肿瘤组织标本(正常组织)、人正常乳腺上皮细胞MCF-10A和人BC细胞(MCF7、SKBR3、MDA-MB-231细胞)中miR-148b-3p和FOXO4的表达情况。对MDA-MB-231细胞进行转染并将其分为对照组(Ctrl组)、inhibitor-NC组、miR-148b-3p inhibitor组、si-NC组、si-FOXO4组、miR-148b-3p inhibitor+si-NC组、miR-148b-3p inhibitor+si-FOXO4组。采用细胞计数试剂盒8(cell counting kit 8,CCK-8)法检测细胞增殖;流式细胞术检测细胞凋亡;透射电镜观察细胞自噬;蛋白质印迹法检测细胞FOXO4、增殖、凋亡和自噬相关蛋白表达;双荧光素酶报告基因检测(double luciferase reporter gene assay,DLR)和miRNA下拉实验验证miR-148b-3p与FOXO4的靶向作用关系。结果:与正常组织比较,BC组织中miR-148b-3p表达升高,FOXO4 mRNA表达降低(P<0.05);Pearson相关性分析结果显示BC患者癌组织中miR-148b-3p的表达水平与FOXO4 mRNA的水平呈负相关(r=−0.774,P<0.01)。与MCF-10A细胞比较,MCF-7细胞、SKBR3细胞和MDA-MB-231细胞中miR-148b-3p表达均升高,FOXO4蛋白和mRNA表达均降低(均P<0.05),且MDA-MB-231细胞中升高或降低更多。miR-148b-3p靶向负调控FOXO4的表达。敲减miR-148b-3p后MDA-MB-231细胞活力、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白水平降低,凋亡率、自噬小体数量、FOXO4蛋白和mRNA水平、cleaved-caspase-3、cleaved-PARP-1、LC3-II/LC3-I、Beclin-1蛋白水平均升高(均P<0.05),而敲减FOXO4后与之相反;敲减FOXO4可减弱敲减miR-148b-3p对MDA-MB-231细胞增殖、凋亡和自噬的影响。结论:miR-148b-3p可能通过靶向FOXO4促进MDA-MB-231细胞增殖,抑制其凋亡和自噬。 展开更多
关键词 miR-148b-3p 叉头框蛋白O4 乳腺癌 增殖 凋亡 自噬
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