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首页> 外文期刊>Pancreatology: official journal of the International Association of Pancreatology (IAP) ... [et al.] >Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells.
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Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells.

机译:吉西他滨诱导VMP1介导的自噬途径来促进人胰腺癌细胞的凋亡性死亡。

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摘要

BACKGROUND/AIM: Autophagy is a degradation process of cytoplasmic cellular constituents. We have described the vacuole membrane protein-1 (VMP1) whose expression triggers autophagy in mammalian cells. The aim of this study was to analyze the role of autophagy in human pancreatic cancer cell death. METHODS/RESULTS: Here we show that gemcitabine, the standard chemotherapy for pancreatic cancer, induced autophagy in PANC-1 and MIAPaCa-2 cells, as evidenced by the accumulation of acidic vesicular organelles, the recruitment of microtubule-associated protein-1 light chain-3, and electron microscopy. In addition, gemcitabine treatment induced early expression of VMP1 in cancer cells. Gemcitabine also induced apoptosis detected by morphology, annexin V-positive cells, and cleavage of caspase-3. Surprisingly, 3-methyladenine, an autophagy inhibitor, decreased apoptosis in gemcitabine-treated cells, showing that autophagy leads to cancer cell apoptotic death. Finally, VMP1 knockdown decreased autophagy and apoptosis in gemcitabine-treated cancer cells. CONCLUSIONS: The VMP1-autophagy pathway promotes apoptosis in pancreatic cancer cells and mediates gemcitabine-induced cytotoxicity. and IAP.
机译:背景/目的:自噬是细胞质细胞成分的降解过程。我们已经描述了液泡膜蛋白-1(VMP1),其表达在哺乳动物细胞中触发自噬。这项研究的目的是分析自噬在人类胰腺癌细胞死亡中的作用。方法/结果:在这里我们显示,吉西他滨是胰腺癌的标准化学疗法,可诱导PANC-1和MIAPaCa-2细胞自噬,其表现为酸性小泡细胞器的积累,微管相关蛋白1轻链的募集。 -3和电子显微镜。另外,吉西他滨治疗诱导了VMP1在癌细胞中的早期表达。吉西他滨还诱导通过形态学,膜联蛋白V阳性细胞和caspase-3裂解检测到的凋亡。令人惊讶的是,自噬抑制剂3-甲基腺嘌呤减少了吉西他滨处理的细胞的凋亡,表明自噬导致癌细胞凋亡性死亡。最后,VMP1敲低减少了吉西他滨治疗的癌细胞中的自噬和凋亡。结论:VMP1自噬途径促进胰腺癌细胞凋亡并介导吉西他滨诱导的细胞毒性。和IAP。

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