Abstract: Objective To investigate the effects of Vitexicarpin on the proliferation of liver cancer cells and its molecular mechanisms. Methods MTS assay and clonogenic formation assay were used to detect the effects of different concentrations of Vitexicarpin (0.5, 1.0 and 2.0 μmol/L, respectively) on the growth of liver cancer cell lines SNU⁃368 and SNU⁃739, as well as human liver immortalized cells THLE⁃2, the appropriate concentration of Vitexicarpin in treatment of liver cancer cells was selected at the same time. Liver cancer cell lines SNU⁃368 and SNU⁃739 were infected with HIF⁃1α overexpressing lentivirus and its negative control lentivirus, while the liver cancer cells overexpressing HIF⁃1α were treated with the appropriate concentration of Vitexicarpin. The expressions of HIF⁃1α, C⁃MYC, and P53 in liver cancer cell lines were detected by qRT⁃PCR and Western blot. The conditions of glycolysis and oxidative phosphorylation in liver cancer cells were analyzed by glucose uptake level, lactate production level, extracellular pH, and cellular oxygen consumption test. The proliferation of the cells was detected by MTS assay and clone formation assay. Results The proliferation of SNU⁃368 and SNU⁃739 cells was inhibited by Vitexicarpin with a dose and time dependent manner. After treatment with 1.0 μmol/L Vitexicarpin, the value of glucose uptake and lactate production in SNU⁃368 and SNU⁃739 liver cancer cells were reduced (all P<0.01), while the extracellular pH and cellular oxygen consumption rate were increased (all P<0.01), and the expression of HIF⁃1α was inhibited (P<0.05). Overexpression of HIF⁃1α could promote the glycolysis of liver cancer cells, inhibit oxidative phosphorylation, and enhance cell proliferation (all P<0.05), while the Vitexicarpin could reverse the growth⁃promoting effect of HIF⁃1α overexpression in liver cancer cells (all P<0.05). Conclusions Vitexicarpin can inhibit the proliferation of cell glycolysis and enhance oxidative phosphorylation by inhibiting the expression of HIF⁃1α, thereby inhibiting the proliferation of liver cancer cells.

Key words: Liver cancer cell；Vitexicarpin；HIF?1α；Proliferation；Reprogramming of glucose metabolism ,