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2β-羟基熊果酸的合成及其抗肿瘤活性
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作者 黄丽荣 陈磊 +3 位作者 杨小生 马琳 张建新 王道平 《应用化学》 CAS CSCD 北大核心 2013年第10期1133-1138,共6页
以熊果酸为原料,经C-3羟基氧化、C-28羧基苄酯化保护、C-2乙酰化及水解、还原、脱保护得到2β-羟基熊果酸,6步反应的总收率为60.1%。中间体及目标化合物结构经IR、1H NMR、13C NMR和MS测试技术确证。以噻唑蓝(MTT)比色法检测2β-羟基熊... 以熊果酸为原料,经C-3羟基氧化、C-28羧基苄酯化保护、C-2乙酰化及水解、还原、脱保护得到2β-羟基熊果酸,6步反应的总收率为60.1%。中间体及目标化合物结构经IR、1H NMR、13C NMR和MS测试技术确证。以噻唑蓝(MTT)比色法检测2β-羟基熊果酸对人白血病细胞K562及人肺癌细胞A549肿瘤细胞的体外抑制活性,结果表明,对2种肿瘤细胞的生长均表现出一定的抑制作用。 展开更多
关键词 熊果酸 2β-羟基熊果酸 合成 肿瘤细胞抑制活性
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In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles 被引量:9
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作者 Li-Cheng Dai Xing Yao +5 位作者 Xiang Wang Shu-Qiong Niu Lin-Fu Zhou Fang-Fang Fu Shui-Xin Yang Jin-Liang Ping 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第16期1966-1972,共7页
AIM:To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.METHODS: HepG2 cell prolifer... AIM:To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.METHODS: HepG2 cell proliferation was analyzed in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction (PCR). RESULTS: The in vitro proliferation of HepG2 cells was signif icantly inhibited by the nanoparticles packaged with MK-ASODNs (NANO-ASODNs). Furthermore, the NANO- ASODNs signif icantly inhibited the growth of HCC in the mouse model. CONCLUSION: NANO-ASODNs can significantly suppress the growth of HCC in vitro and in vivo. 展开更多
关键词 MIDKINE NANOPARTICLES Hepatocellular carcinoma INHIBITION Drug delivery
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Inhibitory effects of grape procyanidins on free radical-induced cell damage in rat hepatocytes in vitro 被引量:10
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作者 Jin-Yi Zhong Hong-Qun Cong Li-Hua Zhang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第19期2752-2755,共4页
AIM: To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS: Normal rat hepatocytes as well as cells damaged by ethanol or ca... AIM: To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS: Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS: Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups (0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05). In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION: Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation. 展开更多
关键词 Grape procyanidin Free radical Cell proliferation Apoptosis HEPATOCYTE
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miRNA studies in in vitro and in vivo activated hepatic stellate cells 被引量:12
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作者 Gunter Maubach Michelle Chin Chia Lim Henry Yang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第22期2748-2773,共26页
AIM: To understand which and how different miRNAs are implicated in the process of hepatic stellate cell (HSC) activation. METHODS: We used microarrays to examine the differential expression of miRNAs during in vitro ... AIM: To understand which and how different miRNAs are implicated in the process of hepatic stellate cell (HSC) activation. METHODS: We used microarrays to examine the differential expression of miRNAs during in vitro activation of primary HSCs (pHSCs). The transcriptome changes upon stable transfection of rno-miR-146a into an HSC cell line were studied using cDNA microarrays. Selected differentially regulated miRNAs were investigated by quantitative real-time polymerase chain reaction during in vivo HSC activation. The effect of miRNA mimics and inhibitor on the in vitro activation of pHSCs was also evaluated.RESULTS: We found that 16 miRNAs were upregulated and 26 were downregulated significantly in 10-d in vitro activated pHSCs in comparison to quiescent pHSCs. Overexpression of rno-miR-146a was characterized by marked upregulation of tissue inhibitor of metalloproteinase-3, which is implicated in the regulation of tumor necrosis factor-α activity. Differences in the regulation of selected miRNAs were observed comparing in vitro and in vivo HSC activation. Treatment with miR-26a and 29a mimics, and miR-214 inhibitor during in vitro activation of pHSCs induced significant downregulation of collagen type Ⅰ transcription. CONCLUSION: Our results emphasize the different regulation of miRNAs in in vitro and in vivo activated pHSCs. We also showed that miR-26a, 29a and 214 are involved in the regulation of collagen type I mRNA. 展开更多
关键词 Hepatic stellate cells MIRNA MIR-146A Nuclear factor-κB
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Inhibitory effect of parvovirus H-1 on the formation of colonies of human hepatoma cell line in vitro and its tumors in nude mice 被引量:1
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作者 YAN SHANGJUN CHENGWU MA +2 位作者 XIANHUA CHEN SHANHONG WAN ZUYU LUO(Physiology and Biophysics Department, Fudan University,Shanghai 200433, China) 《Cell Research》 SCIE CAS CSCD 1994年第1期47-56,共10页
The inhibitory effect of parvovirus H-1 on the colonyforming ability in vitro of QGY-7703, a cultured human hepatoma cell line, and on the formation and growth of its tumors in nude mice was studied. With higher multi... The inhibitory effect of parvovirus H-1 on the colonyforming ability in vitro of QGY-7703, a cultured human hepatoma cell line, and on the formation and growth of its tumors in nude mice was studied. With higher multiplicity of infection (MOI) of H-1 given, survival of the QGY-7703 cells was found to be decreased. H-1 DNA amplification level at 30 h postinfection(p.i.) was detected to be 7.4 times higher than that at 2 h by dispersed cells assay, while the cells were delayed to enter into S phase.Plaques were formed in the indicator cells (new-born human kidney cell line, NBK) by progeny H-1 virus particles released from the infected QGY-7703 cells by infectious cell center assay. The formation of tumors in nude mice by QGY-7703 cells which were injected s c at 2 h postinfection was observed to be prevented in 2 groups with given MOI 25 and 50. The tumor growth of MOI 10 group occurred at a lower exponential rate than that of control,after a 20 d latent period. It was evident that parvovirus H-1 exhibited a direct inhibitory effect on the formation and growth of human hepatoma cells in vivo as well as in vitro. 展开更多
关键词 Parvovirus H-1 human hepatoma cell line colony formation nude mice inhibitory effect
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rmhTNF-α Combined with Cisplatin Inhibits Proliferation of A549 Cell Line In Vitro 被引量:2
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作者 Le-min Xia Yi-yang Zhou 《Chinese Medical Sciences Journal》 CAS CSCD 2014年第3期185-187,共3页
Objective To explore the inhibitory effect of recombinant mutant human tumor necrosis factor-α(rmhTNF-α) in combination with cisplatin on human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma c... Objective To explore the inhibitory effect of recombinant mutant human tumor necrosis factor-α(rmhTNF-α) in combination with cisplatin on human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma cell line A549 was treated with varying concentrations of rmhTNF-α(0.38, 0.75, 1.50, 6.00 and 12.00 IU/ml) or cisplatin(3.91, 7.81, 15.63, 31.25 and 62.50 μg/ml) for 24 hours. Viable cell number was analyzed by using crystal violet staining. The inhibitory rates of A549 cells growth by the two drugs were calculated. For analyzing whether there was a synergistic effect of rmhTNF-α with cisplatin, A549 cells were treated with 0.75 IU/ml rmhTNF-α and increased concentrations of cisplatin. Results rmhTNF-α or cisplatin inhibited the growth of A549 cell lines in a dose-dependent manner. The inhibitory effect of rmhTNF-α combined with cisplatin was significantly greater than cisplatin alone at the same concentration(all P<0.01). Conclusion rmhTNF-α combined with cisplatin might have synergistic inhibitory effect on human lung adenocarcinoma cell line A549. 展开更多
关键词 recombinant mutant human tumor necrosis factor-α CISPLATIN A549 cell line
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Proliferation inhibition of human cervical cancer HeLa cells by Casticin in vitro 被引量:1
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作者 Jing Xie Jun Bai +2 位作者 Xifeng Sheng Jianguo Cao Wanyu Xie 《The Chinese-German Journal of Clinical Oncology》 CAS 2011年第1期47-50,共4页
Objective: The aim of the study was to investigate the effect of Casticin on proliferation inhibition of human cervical cancer HeLa cells in vitro and to unravel the associated mechanisms. Methods: Human cervical He... Objective: The aim of the study was to investigate the effect of Casticin on proliferation inhibition of human cervical cancer HeLa cells in vitro and to unravel the associated mechanisms. Methods: Human cervical HeLa cells were cultured in vitro. The inhibitory effect of Casticin on the viability of human cervical cancer HeLa ceils was evaluated by the MTT assay. The colony formation ability was detected by plate colony formation assay. Distribution of cell cycle was analyzed by flow cytometry. The protein expression levels were analyzed by Western blot. Results: Casticin significantly inhibited the growth of human cervical cancer HeLa cells in a dose- and time-dependent manner, and the IC50 was 2.82 μg/mL. The colony-forming rate was reduced drastically compared with control group (P 〈 0.05). The cells were markedly arrested at G2/M phase after the treatment of Casticin for 48 h. Western blot showed that the expression of p21 protein was up-regulated and protein level of Cyctin B1 was depressed by Casticin in a concentration dependent manner. Conclusion: Casticin could inhibit the cell growth and lead to cell arrest in human cervical cancer HeLa cells, and the down-regulation of Cyclin B1 protein expression and activation of p21 protein might contribute to Casticin induced cell arrest in human cervical cancer HeLa cells. 展开更多
关键词 cervical cancer CASTICIN cyclin B1 P21 PROLIFERATION
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The inhibiting effects of Laggera alata flavone on human ovarian cancer HO-8910 cells proliferation and its mechanism in vitro
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作者 Min Tang Jun Bai +3 位作者 Chunyan Chen Yingxia Ning Xiaochun Li Hanzhen He 《The Chinese-German Journal of Clinical Oncology》 CAS 2014年第9期427-431,共5页
The purpose of this study was to investigate the effect of Laggera alata flavonen (LAF) on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods: H... The purpose of this study was to investigate the effect of Laggera alata flavonen (LAF) on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods: Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibitory effect of LAF on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptotic effect of different concentrations of LAF on HO-8910 cells was assessed by AO/EB staining and FCM with propidium iodide (PI) staining. Expression of proteins related to apoptosis was analyzed by Western blot. Results: LAF significantly inhibited the viability of HO-8910 cells proliferation in a dose-dependent and time-dependent manner, there were statistical significance compared with NS group (P 〈 0.05), and the ICso was 4.28 pg/mL for 48 h. The cells treated with LAF showed typical morphological change and apoptotic rate increased by FCM in a dose-dependent, and there was notable dif- ference compared with NS group (P 〈 0.05). Western blot showed that expression of Fas, caspase-8, tBid and Cyto-c proteins were up-regulated after treatment with LAF for 48 h in a concentration dependent. Conclusion: LAF could inhibit HO-8910 cells proliferation and induce apoptosis, which may be through the pathway of death receptor in vitro. 展开更多
关键词 ovarian cancer Laggera alata flavonen (LAF) APOPTOSIS
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Antisense EGFR sequence reverses the growth properties of human liver carcinoma cell line BEL-7404 in vitro
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作者 XU YONGHUA, WANLI JTANG, SUFENG PENG, YINGHUA CHENLaboratory of Cellular and Molecular Oncology, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China 《Cell Research》 SCIE CAS CSCD 1993年第1期75-83,共9页
A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared wi... A recombinant plasmid containing a full length human epidermal growth factor receptor (EGFR) cDNA sequence in antisense orientation was transferred into cells of a human liver carcinoma cell line BEL-7404. Compared with the control cell clone JX-0 transferred with the vector plasmid and the parent BEL-7404 cells, the antisense EGFR transferred cell clone JX-1 showed a decreased EGFR gene expression and reduced significantly the growth potential either in anchorage-dependent or anchorage-independent growth. Furthermore. JX-1 cells appeared to be distinctly dependent on serum concentration for monolayer growth. The results suggested that antisense EGFR could partly block the EGFR gene ex-pression and reverse the malignant growth properties of human liver carcinoma cells in vitro. 展开更多
关键词 antisense EGFR liver carcinoma cells cell growth
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维甲酸/聚乙二醇磷脂酰乙醇胺胶束的制备及优化
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作者 吕慧敏 齐宪荣 娄晋宁 《中国药学杂志》 CAS CSCD 北大核心 2010年第19期1479-1483,共5页
目的制备甲氧基聚乙二醇磷脂酰乙醇胺(mPEG-DSPE)两亲线型聚合物及其载全反式维甲酸(ATRA)的胶束,通过考察胶束的电位、粒径、包封率进行制备工艺的优化。方法选择多种制备方法及不同药物/聚合物比例制备ATRA胶束。用荧光探针技术测定... 目的制备甲氧基聚乙二醇磷脂酰乙醇胺(mPEG-DSPE)两亲线型聚合物及其载全反式维甲酸(ATRA)的胶束,通过考察胶束的电位、粒径、包封率进行制备工艺的优化。方法选择多种制备方法及不同药物/聚合物比例制备ATRA胶束。用荧光探针技术测定临界胶束浓度(CMC),动态光散射(DLS)法测定其粒径及电位,紫外分光光度法对胶束的载药等性质进行表征,Sulforhodamine B(SRB)法考察载药聚合物胶束及游离ATRA对Balb/c脑内皮细胞的抑制作用。结果药物/聚合物比例对胶束粒径及包封率的影响显著,在药物/聚合物的比例为1∶20时,胶束的粒径约为100nm,包封率为17.47%。mPEG-DSPE聚合物载ATRA胶束可以明显增加ATRA在水中的溶解度,抑制细胞生长的能力约为游离ATRA的29倍。结论两亲性聚合物mPEG-DSPE的胶束对疏水药物ATRA有良好的装载能力,可以显著增加ATRA的溶解度,聚合物胶束能增强ATRA体外细胞毒作用。 展开更多
关键词 甲氧基聚乙二醇磷脂酰乙醇胺 全反式维甲酸 胶束 体外细胞抑制
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Inhibiting effects of low-molecular weight heparin and adrenocortical hormone on hemolysis of red cells in patients with paroxysmal nocturnal hemoglobinuria in vitro 被引量:1
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作者 赵明峰 邵宗鸿 +7 位作者 刘鸿 曹铮 田鹏 付蓉 施均 何广胜 白洁 杨天楹 《Chinese Medical Journal》 SCIE CAS CSCD 2002年第11期1620-1623,145-146,共4页
OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METH... OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone. 展开更多
关键词 DEXAMETHASONE Dose-Response Relationship Drug Hemoglobinuria Paroxysmal HEMOLYSIS Heparin Low-Molecular-Weight Humans Partial Thromboplastin Time
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Antineoplastic mechanism of Octreotide action in human hepatoma 被引量:4
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作者 陈绪军 刘志苏 艾中立 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第11期47-50,106,共5页
Objectives To investigate whether apoptosis can be induced by Octreotide in human hepatoma cells in vitro and elucidate the antineoplastic mechanism of Octreotide in hepatoma.Methods A cultured human hepatoma cell lin... Objectives To investigate whether apoptosis can be induced by Octreotide in human hepatoma cells in vitro and elucidate the antineoplastic mechanism of Octreotide in hepatoma.Methods A cultured human hepatoma cell line,BEL-7402,was exposed to Octreotide and apoptosis was evaluated by cytochemical staining(Hochesst 33258),transmission electron microscopy,agarose gel electrophoresis and flow cytometry(FCM).Results After exposure to 0.2 μg/ml Octreotide,apoptosis with nuclear chromatin condensation as well as fragmentation,cell shrinkage and the formation of apoptotic bodies was observed using cytochemical staining and transmission electron microscopy.A DNA ladder in agarose gel electrophoresis was also displayed.FCM showed that the apoptotic cell number rose with an increase in the concentration of Octreotide(0- 2 iμg/ml).There was a positive correlation between Octreotide concentration and apoptotic rate in BEL-7402 cells(r=0.809,P<0.05).Conclusion Apoptosis in human hepatoma cells can be induced by Octreotide,which may be related to the mechanism of antineoplastic action of Octreotide in hepatoma. 展开更多
关键词 Octreotide liver neoplasm · apoptosis · in vitro · antineoplastic mechanism
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Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro 被引量:7
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作者 SHENG MiaoMiao ZHONG Ying +11 位作者 CHEN Yang DU JianChao JU XiangWu ZHAO Chen ZHANG GuiGen ZHANG LiFang LIU KangTai YANG Ning XIE Peng LI DangSheng ZHANG Michael Q. JIANG ChengYu 《Science China(Life Sciences)》 SCIE CAS 2014年第10期959-972,共14页
Ebola virus (EBOV) causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein (GP... Ebola virus (EBOV) causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein (GP) mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs (miRNAs) in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we report that the miRNAs hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells (HUVECs) following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor (TFPI), dystroglycan! (DAG1) and the caspase 8 and FADD-like apoptosis regulator (CFLAR) were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics. 展开更多
关键词 Ebola virus GLYCOPROTEIN MICRORNAS CYTOTOXICITY
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In vitro inhibitory and pro-apoptotic effect of Stellera Chamaejasme LExtract on human lung cancer cell line NCI-H157 被引量:8
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作者 Xiaoni Liu Yujie Li +5 位作者 Qing Yang Ying Chen Xiaogang Weng Yiwei Wang Ning Li Xiaoxin Zhu 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2012年第3期404-410,共7页
OBJECTIVE:To investigate the inhibitory and pro-apoptotic effect of Stellera Chamaejasme L extract(ESC) in vitro.METHODS:ESC was first extracted with ethanol,and then washed using a polyamide column with 60% ethanol.E... OBJECTIVE:To investigate the inhibitory and pro-apoptotic effect of Stellera Chamaejasme L extract(ESC) in vitro.METHODS:ESC was first extracted with ethanol,and then washed using a polyamide column with 60% ethanol.ESC was then decompressively recycled and vacuum dried at room temperature to obtain active fractions.Subsequently,the cytotoxic and apoptotic effects of ESC on NCI-H157 human lung cancer cells were determined.RESULTS:The results showed that ESC was rich in isomers of Chamaejasminor,neochamaejasmine and Sikokianin.ESC had significant cytotoxicity against NCI-H157 cells,with an IC 50 of approximately 18.50 μg.mL-1.ESC caused significant increase in total apoptotic rate,the activity of caspase 3 and 8,and Fas protein expression(P<0.05).CONCLUSION:The inhibitory effect of ESC on NCI-H157 tumor cells might partly be attributed to its apoptotic induction through activation of the Fas death receptor pathway. 展开更多
关键词 Stellera chamaejasme L Lung neoplasms Apoptosis ANTIGENS CD95 Lissamine rhodamine B
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Adipo8, a high-affinity DNA aptamer, can differentiate among adipocytes and inhibit intracellular lipid accumulation in vitro
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作者 Ke Chen Jun Liu +3 位作者 Guoxiang Tong Bo Liu Guodong Wang Huixia Liu 《Science China Chemistry》 SCIE EI CAS CSCD 2015年第10期1612-1620,共9页
Obesity is primarily caused by the excessive accumulation of white adipose tissues(WAT). We previously obtained an adipocyte-specific aptamer termed Adipo8 in vitro. In this present study, this adipocyte-specific apta... Obesity is primarily caused by the excessive accumulation of white adipose tissues(WAT). We previously obtained an adipocyte-specific aptamer termed Adipo8 in vitro. In this present study, this adipocyte-specific aptamer Adipo8 was first chemically modified by introduction of phosphorothioate linkages(PS-linkages) and then conjugated to polyethylene glycol(PEG), we tested whether this modified aptamer could distinguish mature white adipocytes from 3T3-L1 preadipocytes or brown adipocytes. To verify the binding affinity of this aptamer to mature white adipocytes in vivo as well as in vitro, we tested whether modified Adipo8 could specifically bind to the WAT of Diet-Induced Obesity(DIO) C57BL/6 mice. Finally, we examined the effect of Adipo8 on the adipogenic differentiation of mature white adipocytes. Based on our results, PS-modified aptamer demonstrated its high binding affinity and specificity, and was able to distinguish white adipocytes from 3T3-L1 preadipocytes or brown adipocytes in vitro. PS-modified Adipo8 also demonstrated more biostability and prolonged binding time in biological fluids. Additionally, Adipo8 could inhibit adipogenic differentiation of adipose tissue, possibly by inhibiting the expression of PPAR-γ in adipose tissue. This modified aptamer holds great promise as a stable molecular recognition tool for targeted delivery to adipocytes and has potential in the treatment of obesity. 展开更多
关键词 DNA aptamer ADIPOCYTE modification adipogenic PPAR-Γ
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