Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells

Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells
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自噬在人胃癌 SGC-7901 细胞中通过 Akt/mTOR 途径对毒苷 N 诱导的细胞凋亡发挥保护作用

DOI:
10.1007/s12272-018-1049-8
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发表时间:
2018-07
影响因子:
6.7
通讯作者:
Huang F. Y.
Huang F. Y.
中科院分区:
医学2区
文献类型:
--
作者:
Zhao H. G.;Zhou S. L.;Lin Y. Y.;Wang H.;Dai H. F.;Huang F. Y.

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毒素N(Tox N)是一种天然产物,具有诱导人胃癌细胞凋亡的作用。然而,自噬在Tox N诱导人胃癌细胞凋亡中的机制和实际作用尚不清楚。在目前的研究中,我们证明了Tox N可以通过抑制SGC-7901细胞的Akt/mTOR信号通路来诱导自噬。此外,我们还发现自噬抑制剂3-甲基腺嘌呤对自噬的抑制作用增强了Tox N诱导的细胞死亡。然而,自噬激活剂雷帕霉素对自噬的刺激作用显著抑制了Tox N诱导的细胞凋亡,提示自噬在Tox N诱导的细胞凋亡中起保护作用。因此,本研究结果表明,Tox N与自噬抑制剂联合使用可能是一种有希望的策略,以增强Tox N的抗癌活性,用于治疗人胃癌。
Toxicarioside N (Tox N), a natural product extract fromAntiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.
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