¹²⁵I Radioactive Particles Drive Protective Autophagy in Hepatocellular Carcinoma by Upregulating ATG9B

¹²⁵I radioactive particles implantation have demonstrated efficacy in eradicating hepatocellular carcinoma (HCC). However, progressive resistance of HCC to ¹²⁵I radioactive particles has limited its wide clinical application.

We investigated the cellular responses to ¹²⁵I 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.

In this study, we demonstrated that ¹²⁵I radioactive particles induced cell apoptosis and protective autophagy of HCC in vitro and in vivo. Inhibition of autophagy enhanced the radiosensitivity of HCC to ¹²⁵I radioactive particles. Moreover, ¹²⁵I 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 ¹²⁵I radioactive particles in vitro and in vivo.

Inhibition of ATG9B enhanced the antitumor effects of ¹²⁵I particle radiation against HCC in vitro and in vivo. Our findings suggest that ¹²⁵I particle radiation plus chloroquine or/and the ATG9B inhibitor may be a novel therapeutic strategy for HCC.