Pakistan Journal of Pharmaceutical Sciences

Abstract: Berberine (BBR), an isoquinoline alkaloid abundant in Coptis chinensis, exhibits anti-tumor and hypoglycemic properties. The regulation of tumor cell homeostasis and metabolism is greatly influenced by Hypoxia-inducible factor-1? (HIF-1?). This research aims to elucidate whether BBR inhibits the progression of hepatocellular carcinoma (HCC) by modulating HIF-1? expression. Simulating the tumor hypoxic microenvironment in vitro by CoCl2 addition to induce the HIF-1? expression. The optimal concentration of BBR and CoCl2 were screened by CCK-8 assay. Clone formation, wound healing, EDU staining, Transwell assay, and flow cytometry evaluated the malignant biological behavior of HepG2 cells. RT-qPCR and Western blot assessed HIF-1? and glycolysis-related protein levels. Finally, the influence of BBR in vivo was investigated by a xenograft tumor model in nude mice. After exposure to 100 ?mol/L BBR, the proliferation, migration and invasion of HepG2 cells were reduced, along with apoptosis was increased, while the levels of glycolysis-related proteins were decreased (P<0.05). 100 ?mol/L CoCl2 treatment increased the level of HIF-1?, promoted the malignant progression of HCC and attenuated the anti-tumor effect of BBR. Additionally, BBR inhibited tumor growth in nude mice. In conclusion, BBR exerts antitumor effects through upregulating HIF-1? and could be used as a therapeutic agent for HCC.