Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer

Zheng-ting Deng ¹Shu-fang Liang ²Guo-kai Huang ²Yu-qian Wang ²Xiao-yu Tu ²Ya-ni Zhang ²Shu Li ³Tao Liu ⁴Bin-bin Cheng²

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作者信息

1. Department of Respiration,Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine,Taizhou 225300,Jiangsu Province,China;Oncology Department of Traditional Chinese Medicine,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China;Department of Febrile Diseases,School of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing210023,Jiangsu Province,China
2. Oncology Department of Traditional Chinese Medicine,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China
3. Department of Gastroenterology,Baoshan Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201900,China
4. Department of Febrile Diseases,School of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing210023,Jiangsu Province,China
折叠

Abstract

Objective:The effects of arsenic trioxide(As2O3)on hepatocellular carcinoma have been documented widely.Autophagy plays dual roles in the survival and death of cancer cells.Therefore,we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells.Methods:The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum.The rate of apoptosis in liver cancer cells treated with As2O3 was evaluated using flow cytometry,Hoechst 33258 staining,and TUNEL assays.The rate of autophagy among liver cancer cells treated with As2O3 was detected using immunofluorescence,Western blot assay and transmission elec-tron microscopy.Results:Upon treatment with As2O3,the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner.The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3,as shown by flow cytometry.Apoptosis in liver cancer cells treated with As2O3 was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression.Furthermore,As2O3 treatment induced autophagy in liver cancer cells;this finding was supported by Western blot,immunofluorescence of LC3-Ⅱ and beclin 1,and transmission electron microscopy.In liver cancer cells,As2O3 inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapa-mycin(PI3K/AKT/mTOR)signal pathway that plays a vital role in both apoptosis and autophagy.The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis.Furthermore,inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3 on cell viability.Serum starvation increased autophagy and amplified the effect of As2O3 on cell death.Conclusion:As2O3 induces apoptosis and autophagy in liver cancer cells.Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells.This study provides novel insights into the effects of As2O3 against liver cancer.

Key words

Apoptosis/Arsenic trioxide/Autophagy/Primary liver cancer

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基金项目

National Natural Science Foundation of China(82074203)

National Natural Science Foundation of China(82274328)

National Natural Science Foundation of China(81673655)

出版年

2024

结合医学学报(英文版)

上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD

影响因子：0.711

ISSN：2095-4964

参考文献量4

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