Resveratrol inhibited the progression of human hepatocellular carcinoma by inducing autophagy via regulating p53 and the phosphoinositide 3-kinase/protein kinase B pathway

Resveratrol, a natural product, has been revealed to exert antitumor effects in multiple types of tumors. However, the antitumor effects of resveratrol on hepatocellular carcinoma (HCC) and its potential underlying mechanisms have not yet been elucidated. The present study demonstrated that resveratrol inhibited viability, proliferation, invasion and migration of HCC cells significantly in a time- and dose-dependent manner, indicating that resveratrol exerted antitumor effects in HCC. Furthermore, relative expression of autophagy-related proteins Bedin1 and LC3 II/I ratio was increased while p62 expression was decreased by resveratrol treatment dose-dependently. The LC3(+) puncta formation, which represented autophagosome formation was also markedly dose-dependently upregulated by resveratrol treatment, suggesting that resveratrol induced autophagy in HCC cells. In addition, treatment with autophagy inhibitor 3 -methyladenine (3-MA) counteracted the inhibitory effect of resveratrol on HCC cell proliferation, invasion and migration, indicating that suppressing autophagy may hamper the antitumor effect of resveratrol in HCC. It was revealed that resveratrol upregulated the expression of p53 while decreasing the ratio of phosphorylated protein kinase B (p-Akt)/Akt in HCC cells. Treatment with p53 inhibitor pifithrin-alpha and Akt activator insulin-like growth factor-1 decreased the expression of Beclin1 while significantly promoting cell proliferation, invasion and migration compared with the resveratrol treatment group. Taken together, the results of the present study revealed that resveratrol inhibited the proliferation and mobility of HCC cells through inducing autophagy via activating p53 and inhibiting phosphoinositide 3-kinase/Akt. Enhancing autophagy can augment the antitumor effects of resveratrol in HCC. Therefore, combining resveratrol with an autophagy inducer may be a viable option for treating HCC.