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The Study of the Influence of Unfolded Protein Response and Autophagy on Sorafenib-Induced Tumor Inhibition of Hepatocellular Carcinoma

Jian Wu, Qi Zhuang, Xiaojie Gao, Xiongwei Yang, Rili Qin, Liying Zhang, Xinchen Zhang

To study the effects of the unfolded protein response (UPR) activation and autophagy inhibition on sorafenib inducing apoptosis of hepatocellular carcinoma (HCC) cells. We activated UPR of the HepG2 cells by dithiothreitol (DTT) and tunicamycin (Tun). 3-methyladenine was used to inhibit autophagy of HepG2 cells. The proliferation, apoptosis and adhesion ability of HCC cells were tested by MTT assay and flow cytometry, respectively. The invasion and migration abilities of cells were detected by Trans well assay. Moreover, we established HCC orthotopic transplantation tumor model of nude mice. The activation of UPR can inhibit the sorafenib-induced apoptosis of HCC cells. Inhibiting autophagy significantly enhanced the sorafenib-induced apoptosis of HCC cells. Activating the UPR can enhance the sorafenib resistance of HCC cells. On the contrary, inhibiting autophagy causes opposite effects.