J Cancer 2018; 9(23):4314-4324. doi:10.7150/jca.27943

Research Paper

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

Linjing Li1,3*, Xinyue Liu1*, Liye Zhou3, Wei Wang4, Zhuan Liu1, Yan Cheng5, Jing Li1, Hulai Wei2✉

1. Department of Clinical Laboratory Center, The Second Hospital of Lanzhou University, Lanzhou 730000, P.R. China;
2. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P.R. China;
3. Dana-Farber cancer institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215-5450, USA;
4. Marlene and Stewart Greenbaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA;
5. Northwest University for Nationalities, Lanzhou 730000, P.R. China.
*contributed equally to this article

Abstract

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.

Keywords: Insulin resistance, Hepatocellular carcinoma, Autophagy, Endoplasmic reticulum, Chemoresistance

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How to cite this article:
Li L, Liu X, Zhou L, Wang W, Liu Z, Cheng Y, Li J, Wei H. Autophagy Plays a Critical Role in Insulin Resistance- Mediated Chemoresistance in Hepatocellular Carcinoma Cells by Regulating the ER Stress. J Cancer 2018; 9(23):4314-4324. doi:10.7150/jca.27943. Available from http://www.jcancer.org/v09p4314.htm