Resveratrol Promoted Interferon-α-Induced Growth Inhibition and Apoptosis of SMMC7721 Cells by Activating the SIRT/STAT1.

Interferon- (IFN-) resistance is a major hurdle in the treatment of hepatocellular carcinoma (HCC). Signal transducers and activators of transcription 1 (STAT1) play a key role in exerting the antiproliferative and proapoptotic effects of IFN- on tumors. In this study, we aimed to investigate whether resveratrol can promote IFN--induced growth inhibition and the apoptosis on HCC cells through the SIRT/STAT1 pathway. We found that IFN- induced growth inhibition and apoptosis of SMMC7721 cells, and the effects could be significantly enhanced and blocked by resveratrol and EX527, respectively. Resveratrol not only activated SIRT1 but also induced phosphorylation of STAT1. Further study revealed that ablation of STAT1 reduced the combined antitumor effects of IFN- and resveratrol, lowered the rate of apoptosis, and improved the viability of SMMC7721 cells. Whereas STAT1 overexpression strengthened the combined antitumor effects of resveratrol and IFN-. Our findings suggest a novel strategy of using resveratrol to enhance the response of HCC to IFN- treatment through the SIRT/STAT1 pathway.