I 放射性粒子通过上调ATG9B驱动肝细胞癌中的保护性自噬。

I Radioactive Particles Drive Protective Autophagy in Hepatocellular Carcinoma by Upregulating ATG9B.

作者信息

Xiao Yunhua, Yuan Jing, Yang Chongshuang, Xiong Junru, Deng Liangyu, Liang Qinghua, He Chuang, Li Liangshan, He Fengtian, Huang Xuequan

机构信息

Department of Nuclear Medicine, the First Affiliated Hospital of Army Medical University, Army Medical University, Chongqing, China.

Department of Radiology, Army Medical Center, Chongqing, China.

出版信息

J Clin Transl Hepatol. 2023 Apr 28;11(2):360-368. doi: 10.14218/JCTH.2022.00023. Epub 2022 Jun 6.

DOI:10.14218/JCTH.2022.00023

PMID:36643035

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9817064/

Abstract

BACKGROUND AND AIMS

I radioactive particles implantation have demonstrated efficacy in eradicating hepatocellular carcinoma (HCC). However, progressive resistance of HCC to I radioactive particles has limited its wide clinical application.

METHODS

We investigated the cellular responses to I radioactive particles treatment and autophagy-related 9B (ATG9B) silencing in HCC cell lines and Hep3B xenografted tumor model using Cell Counting Kit-8 reagent, western blotting, immunofluorescence, flow cytometry, transmission electron microscopy and immunohistochemistry.

RESULTS

In this study, we demonstrated that I radioactive particles induced cell apoptosis and protective autophagy of HCC and . Inhibition of autophagy enhanced the radiosensitivity of HCC to I radioactive particles. Moreover, I radioactive particles induced autophagy by upregulating ATG9B, with increased expression level of LC3B and decreased expression level of p62. Furthermore, ATG9B silencing downregulated LC3B expression and upregulated p62 expression and enhanced radiosensitivity of HCC to I radioactive particles and .

CONCLUSIONS

Inhibition of ATG9B enhanced the antitumor effects of I particle radiation against HCC and Our findings suggest that I particle radiation plus chloroquine or/and the ATG9B inhibitor may be a novel therapeutic strategy for HCC.

摘要

背景与目的

碘放射性粒子植入已显示出在根除肝细胞癌（HCC）方面的疗效。然而，HCC对碘放射性粒子的渐进性耐药限制了其广泛的临床应用。

方法

我们使用细胞计数试剂盒-8试剂、蛋白质印迹法、免疫荧光法、流式细胞术、透射电子显微镜和免疫组织化学，研究了肝癌细胞系和Hep3B异种移植肿瘤模型中细胞对碘放射性粒子治疗和自噬相关蛋白9B（ATG9B）沉默的反应。

结果

在本研究中，我们证明碘放射性粒子诱导了HCC的细胞凋亡和保护性自噬。抑制自噬增强了HCC对碘放射性粒子的放射敏感性。此外，碘放射性粒子通过上调ATG9B诱导自噬，导致微管相关蛋白轻链3B（LC3B）表达水平增加和p62表达水平降低。此外，ATG9B沉默下调了LC3B表达，上调了p62表达，并增强了HCC对碘放射性粒子的放射敏感性。