Recombinant canstatin inhibits the progression of hepatocellular carcinoma by repressing the HIF-1α/VEGF signaling pathway

Hepatocellular carcinoma (HCC), a hypervascular tumor, is the most frequent primary malignant tumor of the liver. Angiogenesis inhibitors, such as endogenous angiogenesis inhibitors, are essential for HCC therapy and have generated significant interest owing to their safety, efficacy, and multitargeting attributes. Canstatin is an angiogenesis inhibitor derived from the basement membrane and exerts anti-tumor effects. However, the inhibitory effects and underlying mechanisms of action of canstatin on HCC remain unclear. Therefore, in this study, HepG2 and Huh7 cells were used to investigate the inhibitory effects of recombinant canstatin on HCC cells. Subsequently, the biosafety and inhibitory effects of recombinant canstatin on tumor growth were investigated in a xenograft animal model of liver cancer. Canstatin inhibited the growth of liver cancer cells by regulating their proliferation, apoptosis, and migration. Additionally, it suppressed the occurrence and progression of HCC by modulating the HIF-1α/VEGF signaling pathway. In mice, canstatin exerted no discernible harmful side effects and suppressed the growth of HCC subcutaneous xenograft tumors. Overall, our findings shed light on the molecular pathways underlying canstatin-induced HCC cell death that may help develop novel HCC treatments.