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IntroductionHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, particularly in patients with cirrhosis. Genistein (GEN), a tyrosine kinase inhibitor with a favorable safety profile, has potential as a chemoprotective agent in high-risk populations. This study evaluated the effects of GEN in a rat model of diethylnitrosamine (DEN)-induced cirrhosis and HCC.MethodsThirty-three male Sprague Dawley rats were randomized into three groups (n=11/group): Control, HCC, and HCC+GEN. HCC was induced by weekly intraperitoneal DEN injections (70 mg/kg) for 16 weeks. From weeks 8-16, the GEN group received oral genistein (50 mg/kg/day), while other groups received vehicle. Liver tissues were examined histopathologically and immunohistochemically for HCC, caspase-9, ERK-1, α-SMA, and MMP-2. Tumor burden was calculated to reflect tumor size and number. Serum AFP, p53, and biochemical parameters were analyzed.ResultsTumor burden was significantly increased in the HCC group compared with controls and was significantly reduced by GEN treatment (p=0.002). Elevated serum AFP and p53 levels in the HCC group were significantly decreased with GEN. Although cirrhosis developed in both HCC groups, collagen deposition was significantly lower in the GEN-treated rats. GEN treatment was associated with reduced expression of ERK-1, α-SMA, and MMP-2, and increased caspase-9 expression, indicating anti-proliferative, anti-fibrotic, and pro-apoptotic effects.ConclusionsGenistein reduced tumor burden, serum tumor markers, and liver fibrosis in a rat model of HCC, supporting its potential as a chemoprotective agent in cirrhotic livers. Further dose-optimization and clinical studies are warranted.