Pirfenidone Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

• DOI: 10.12659/msm.907891
• Publication Date: 2017-12-25T13:13:06Z
• Authors: Wei-Jie Zou; Zhi Huang; Tian-Peng Jiang; Ya-Ping Shen; An-Su Zhao; Shi Zhou; Shuai Zhang
• Keywords: 0301 basic medicine; 0303 health sciences; Carcinoma, Hepatocellular; Pyridones; Liver Neoplasms; Apoptosis; Cell Count; Hep G2 Cells; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Lab/In Vitro Research; Cell Line, Tumor; Humans; Wnt Signaling Pathway; beta Catenin; Cell Proliferation; Signal Transduction

BACKGROUND Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. MATERIAL AND METHODS In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of β-catenin and p-β-catenin. RESULTS Pirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed b-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the β-catenin activator, SB-216763. The results revealed that SB-216763 accelerated proliferation and inhibited apoptosis in HepG2 cells treated with pirfenidone. Western blot results showed that SB-216763 upregulated β-catenin expression in HepG2 cells treated with pirfenidone. CONCLUSIONS In conclusions, pirfenidone may be a potential drug for HCC treatment.