Autophagy Plays a Critical Role in Insulin Resistance- Mediated Chemoresistance in Hepatocellular Carcinoma Cells by Regulating the ER Stress

The high mortality of hepatocellular carcinoma (HCC) patients is associated with several independent risk factors including type 2 diabetes mellitus (T2DM) and insulin resistance (IR), which could be caused by various pathological processes such as tumorigenesis and inflammation in the liver. In previous report, we declared that IR contributes to multidrug resistance in HCC by activation of endoplasmic reticulum (ER) stress. Here, our study revealed that the enhanced autophagy induced by IR significantly prompts the chemotherapeutic drug resistance in hepatoma cells, which was validated by stimulation and inhibition of the autophagy respectively. A potential reason is that autophagy acts as a regulator of ER stress in the IR-mediated chemoresistance in HCC. In conclusion, autophagy facilitates the HCC survival in chemotherapeutic drug treatment by maintaining the homeostasis in the ER indicating the regulatory role of autophagy in ER stress contributes to IR-mediated chemoresistance in hepatocellular carcinoma cells. Collectively, these data implied inhibition of autophagy is a potential treatment of inherent IR-mediated chemoresistance in HCC.