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20(S)-人参皂苷 Rh2 通过抑制 AMPK/mTOR 通路诱导宫颈癌细胞凋亡和保护性自噬。

20(S)-Ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway.

机构信息

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, China.

出版信息

Biosci Biotechnol Biochem. 2021 Dec 22;86(1):92-103. doi: 10.1093/bbb/zbab189.

DOI:10.1093/bbb/zbab189
PMID:34718401
Abstract

20(S)-Ginsenoside Rh2 (GRh2) has various biological activities including anticancer effects. However, no reports have investigated the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRh2. In this study, we found that 20(S)-GRh2 suppressed proliferation and induced apoptosis in HeLa cells by activating the intrinsic apoptotic pathway and causing mitochondrial dysfunction. 20(S)-GRh2 enhanced cell autophagy through promoting the phosphorylation of AMPK, depressed the phosphorylation of AKT, and suppressed mTOR activity. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3-MA) enhanced 20(S)-GRh2-induced apoptosis, while the autophagy inducer rapamycin promoted cell survival. Moreover, the apoptosis inhibitor Z-VAD-FMK significantly restrained the apoptosis and autophagy induced by 20(S)-GRh2 in HeLa cells. We found that 20(S)-ginsenoside Rh2-induced protective autophagy promotes apoptosis of cervical cancer cells by inhibiting AMPK/mTOR pathway.

摘要

20(S)-人参皂苷 Rh2 (GRh2) 具有多种生物活性,包括抗癌作用。然而,目前尚无报道研究 20(S)-GRh2 处理的 HeLa 细胞中自噬与细胞凋亡之间的关系。在本研究中,我们发现 20(S)-GRh2 通过激活内在凋亡途径和引起线粒体功能障碍来抑制 HeLa 细胞的增殖并诱导细胞凋亡。20(S)-GRh2 通过促进 AMPK 的磷酸化增强细胞自噬,抑制 AKT 的磷酸化,并抑制 mTOR 活性。此外,自噬抑制剂 3-甲基腺嘌呤 (3-MA) 的处理增强了 20(S)-GRh2 诱导的细胞凋亡,而自噬诱导剂雷帕霉素促进了细胞存活。此外,凋亡抑制剂 Z-VAD-FMK 显著抑制了 20(S)-GRh2 在 HeLa 细胞中诱导的凋亡和自噬。我们发现 20(S)-人参皂苷 Rh2 诱导的保护性自噬通过抑制 AMPK/mTOR 通路促进宫颈癌细胞的凋亡。

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