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Autophagy inhibition by reversine and its suppressive effects on human hepatocellular carcinoma cells.
Biochemical and Biophysical Research Communications ( IF 3.1 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.bbrc.2020.05.054
Lingling Zhu 1 , Qiongle Wu 1 , Bin Quan 1 , Jianghua Yang 1 , Jinsun Yang 1 , Weishun Hou 1 , Li Cheng 2
Affiliation  

Introduction

Therapy for human hepatocellular carcinoma (HCC) remains a great challenge for physicians and patients worldwide. The anti-tumor effects of reversine have attracted much more concerns.

Materials and methods

This study evaluated the growth regulatory effects of reversine on HCC cells lines. Meanwhile, the underlying mechanism including autophagy modulation was also identified.

Results

reversine markedly inhibited the proliferation of both HCC cells and induced cell apoptosis and multinuclear in a dose-dependent manner. In addition, the decreased ratio of LC3II/LC3I as well as elevated p62 expression were observed under reversine treatment, indicating the autophagy inhibition by reversine in HepG2 cell line. Moreover, modulation of autophagy with rapamycin and chloroquine significantly attenuated and enhanced the cytostatic effects of reversine, respectively.

Conclusions

reversine could reduce the cell viability of HCC cells via inducing cell apoptosis and polyploidy. In addition, cell autophagy was involved and might play a protective role in HCC cells, the joint use of autophagy inhibitor enhanced reversine-mediating antitumor effects. Our data offered novel ideas for comprehensive therapeutic regimes on human hepatocellular carcinoma.



中文翻译:

可逆性自噬抑制作用及其对人肝癌细胞的抑制作用

介绍

对人类肝细胞癌(HCC)的治疗仍然是全球医师和患者的巨大挑战。可逆的抗肿瘤作用引起了更多的关注。

材料和方法

这项研究评估了可逆对HCC细胞系的生长调节作用。同时,还确定了包括自噬调节在内的潜在机制。

结果

逆转录酶以剂量依赖的方式显着抑制了HCC细胞的增殖并诱导了细胞凋亡和多核细胞。此外,在可逆性处理下观察到LC3II / LC3I比例降低以及p62表达升高,表明可逆性抑制了HepG2细胞系的自噬。此外,雷帕霉素和氯喹对自噬的调节分别显着减弱和增强了可逆性的细胞抑制作用。

结论

可逆可通过诱导细胞凋亡和多倍性降低肝癌细胞的生存能力。此外,细胞自噬也参与其中,并可能在HCC细胞中起保护作用,自噬抑制剂的联合使用增强了可逆介导的抗肿瘤作用。我们的数据为人类肝细胞癌的综合治疗方案提供了新颖的思路。

更新日期:2020-05-23
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