Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环...Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环境的调控,其高表达与多种癌症类型的不良预后显著相关。近期的研究表明,p53也与Hsp90α拥有复杂而密切的联系,二者之间的交互作用对肿瘤的发生发展有十分重要的作用。在本综述中,我们将探讨Hsp90α在癌症发生和治疗中的作用,关注其与p53这一关键肿瘤抑制蛋白的相互作用。展开更多
BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory...BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.展开更多
目的：观察热休克蛋白90α/β（ heat shock protein 90α/β,HSP90α/β）在胃癌组织中的表达及临床意义,为胃癌的早期诊断与分子病理分型提供有价值的实验资料。方法采用免疫组织化学染色结合组织芯片,观察HSP90α/β蛋白质在正常胃...目的：观察热休克蛋白90α/β（ heat shock protein 90α/β,HSP90α/β）在胃癌组织中的表达及临床意义,为胃癌的早期诊断与分子病理分型提供有价值的实验资料。方法采用免疫组织化学染色结合组织芯片,观察HSP90α/β蛋白质在正常胃黏膜组织、癌旁组织及胃癌组织中的表达；然后分析HSP90α/β蛋白质在胃癌组织中表达的临床意义。结果免疫组织化学染色结果显示,胃癌组织中HSP90α/β蛋白质表达的阳性率高于正常胃黏膜组织和癌旁组织（P〈0.05）；癌旁组织中表达的阳性率高于正常胃黏膜组织（P〈0.05）；淋巴结转移患者组织中表达的阳性率高于无淋巴结转移者（P〈0.05）；Ⅲ~Ⅳ期患者组织中表达的阳性率高于Ⅰ~Ⅱ期（P〈0.05）。结论 HSP90α/β蛋白质的表达与胃癌组织的发生、分化程度、淋巴结转移及TNM分期有关,即随着胃癌组织分化程度的降低、淋巴结转移的发生及TNM分期的增加而表达升高。展开更多
随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结...随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结合的方法,鉴定了IMRT和IMR90细胞中的差异蛋白质和差异代谢物。结果表明:在IMRT细胞中,重要代谢通路的蛋白质水平发生变化,如葡萄糖磷酸变位酶1(PGM1)、6-磷酸葡萄糖脱氢酶(G6PD)、谷胱甘肽过氧化物酶1(GPX1)、谷胱甘肽S-转移酶M2(GSTM2)等。相关通路中的代谢物,如6-磷酸葡萄糖,肉碱,磷酸胆碱,亮氨酸异亮氨酸,谷氨酰胺和丙氨酸的含量有显著变化。结合分析结果,我们在IMR90中沉默GPX1基因,促进了IMR90的衰老进程,表明GPX1在细胞衰老进程中的重要作用。展开更多
文摘Hsp90 (Heat Shock Protein 90)是一种在细胞应激条件下诱导表达的分子伴侣蛋白,在发现其可以作为癌症的诊断手段及治疗靶点后,其研究迎来了井喷式的发展。已有研究表明,Hsp90α不仅与肿瘤细胞的生存、增殖和迁移有关,还参与了肿瘤微环境的调控,其高表达与多种癌症类型的不良预后显著相关。近期的研究表明,p53也与Hsp90α拥有复杂而密切的联系,二者之间的交互作用对肿瘤的发生发展有十分重要的作用。在本综述中,我们将探讨Hsp90α在癌症发生和治疗中的作用,关注其与p53这一关键肿瘤抑制蛋白的相互作用。
基金Supported by Health Commission of Qinghai Province,No.2021-wjzdx-18.
文摘BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.
文摘随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结合的方法,鉴定了IMRT和IMR90细胞中的差异蛋白质和差异代谢物。结果表明:在IMRT细胞中,重要代谢通路的蛋白质水平发生变化,如葡萄糖磷酸变位酶1(PGM1)、6-磷酸葡萄糖脱氢酶(G6PD)、谷胱甘肽过氧化物酶1(GPX1)、谷胱甘肽S-转移酶M2(GSTM2)等。相关通路中的代谢物,如6-磷酸葡萄糖,肉碱,磷酸胆碱,亮氨酸异亮氨酸,谷氨酰胺和丙氨酸的含量有显著变化。结合分析结果,我们在IMR90中沉默GPX1基因,促进了IMR90的衰老进程,表明GPX1在细胞衰老进程中的重要作用。
