IGF-1 Inducing Autophagy Promotes Hepatocellular Carcinoma Growth And Metastasis

BACKGROUND: Hepatocellular carcinoma(HCC)is one of the most common cancers in the world with high morbidity,high mortality and poor prognosis.Diabetes mellitus(DM)is one of the independent risk factors for the onset of HCC.Studies have shown that at the time of diabetes,due to endocrine disorders,a variety of growth factors including IGF-1 expressed abnormally,which plays a key role in promoting tumor growth and survival.A number of studies have found that autophagy is also involved in the occurrence and development of tumors,but autophagy is still controversial in whether promoting or inhibiting tumor growth,and the cause of changes in autophagy levels during tumorigenesis is not yet clear.OBJECTIVE: To study whether the expression of IGF-1 and the level of autophagy are abnormal in HCC patients with diabetes.And further study the correlation between IGF-1 and autophagy.The effect of IGF-1 on autophagy is related to the biological behaviors such as proliferation,migration and invasion of hepatocellular cells.METHODS:(1)Forty patients with HCC and 40 patients with HCC as well as diabetes were collected.Tumor and para-tumor tissues were collected.The gene expression levels of IGF-1 and autophagy-related proteins were detected by PCR.(2)HepG2 cell lines were cultured in vitro and then stimulated by IGF-1(insulin-like growth factor 1)to simulate diabetic microenvironment of inflammation,and treated with autophagy inhibitor(Wortmannin)to detect autophagy-related protein expression and biological behaviors such as cell proliferation,apoptosis,and invasion.RESULTS: We found that the expression of IGF-1 in HCC tissues was higher than in normal liver tissues and even higher in HCC patients with DM.The level of autophagy-related proteins in HCC tumors is different,especially in HCC patients with DM.In vitro experiments,we found that IGF-1 can promote autophagy,thereby inhibiting the apoptosis of HCC cells and inducing cell growth and migration.These results suggest that IGF-1 may be involved in tumor progression by inducing autophagy and may be a potential therapeutic target for HCC.