Autophagy inhibition augments resveratrol-induced apoptosis in Ishikawa endometrial cancer cells.
Autophagy inhibition augments resveratrol-induced apoptosis in Ishikawa endometrial cancer cells.
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DOI：
10.3892/ol.2016.4978
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发表时间：
2016-10
期刊：
影响因子：
2.9
通讯作者：
Fujii T
中科院分区：
文献类型：
--
作者：
Fukuda T;Oda K;Wada-Hiraike O;Sone K;Inaba K;Ikeda Y;Makii C;Miyasaka A;Kashiyama T;Tanikawa M;Arimoto T;Yano T;Kawana K;Osuga Y;Fujii T
白藜芦醇(RSV)是一种从红酒中提取的多酚化合物，可抑制多种癌症的增殖。RSV诱导癌细胞的凋亡，同时增强自噬。自噬通过推动细胞代谢来促进癌细胞生长，这可能会抵消RSV的影响。本研究旨在阐明RSV与自噬的关系，以及抑制自噬是否可以增强RSV在子宫内膜癌细胞中的抗肿瘤作用。采用四甲基偶氮唑盐比色法、流式细胞术和膜联蛋白V染色分别检测RSV暴露后Ishikawa子宫内膜癌细胞株的细胞增殖、细胞周期进程和细胞凋亡。通过Western blotting和免疫荧光检测自噬标志物轻链3，II的表达水平来评价自噬。用氯喹(CQ)和针对自噬相关基因5(ATG5)或7(ATG7)的小干扰RNA抑制自噬，并用四甲基偶氮唑盐比色法检测其与RSV的联合作用。RSV对石川细胞的增殖抑制作用呈剂量依赖性。此外，RSV暴露增加了亚G1期细胞的丰度，并诱导了细胞凋亡。在RSV处理后观察到LC3-II的积累，这表明RSV诱导了自噬。与RSV单独处理相比，CQ和RSV联合处理对细胞生长抑制和细胞凋亡的抑制作用更强。下调ATG5或ATG7的表达可显著增强RSV诱导的细胞凋亡。本研究结果表明，RSV诱导的自噬可能抵消了RSV在石川细胞中的抗肿瘤作用。RSV和自噬抑制剂(如CQ)的联合治疗可能是治疗某些子宫内膜癌细胞的一种有吸引力的治疗选择。
Resveratrol (RSV), a polyphenolic compound derived from red wine, inhibits the proliferation of various types of cancer. RSV induces apoptosis in cancer cells, while enhancing autophagy. Autophagy promotes cancer cell growth by driving cellular metabolism, which may counteract the effect of RSV. The present study aimed to elucidate the correlation between RSV and autophagy and to examine whether autophagy inhibition may enhance the antitumor effect of RSV in endometrial cancer cells. Cell proliferation, cell cycle progression and apoptosis were examined, following RSV exposure, by performing MTT assays, flow cytometry and annexin V staining, respectively, in an Ishikawa endometrial cancer cell line. Autophagy was evaluated by measuring the expression levels of light chain 3, II (LC3-II; an autophagy marker) by western blotting and immunofluorescence. Chloroquine (CQ) and small interfering RNAs targeting autophagy related (ATG) gene 5 (ATG5) or 7 (ATG7) were used to inhibit autophagy, and the effects in combination with RSV were assessed using MTT assays. RSV treatment suppressed cell proliferation in a dose-dependent manner in Ishikawa cells. In addition, RSV exposure increased the abundance of the sub-G1 population and induced apoptosis. LC3-II accumulation was observed following RSV treatment, indicating that RSV induced autophagy. Combination treatment with CQ and RSV more robustly suppressed growth inhibition and apoptosis, compared with RSV treatment alone. Knocking down ATG5 or ATG7 expression significantly augmented RSV-induced apoptosis. The results of the present study indicated that RSV-induced autophagy may counteract the antitumor effect of RSV in Ishikawa cells. Combination treatment with RSV and an autophagy inhibitor, such as CQ, may be an attractive therapeutic option for treating certain endometrial cancer cells.
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影响因子：
3.2
作者：
Gasparrini, Massimiliano;Giampieri, Francesca;Battino, Maurizio
通讯作者：
Battino, Maurizio
影响因子：
11.2
作者：
Opipari, AW;Tan, LJ;Liu, JR
通讯作者：
Liu, JR
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.
影响因子：
3.1
作者：
Borriello, Adriana;Bencivenga, Debora;Della Ragione, Fulvio
通讯作者：
Della Ragione, Fulvio
DOI：
10.1016/j.bbrc.2015.01.034
发表时间：
2015-02-20
影响因子：
3.1
作者：
Chen, Sifan;Zhou, Niman;Zhu, Wei
通讯作者：
Zhu, Wei