Effect and Its Mechanism of Lovastatin Combined with Cisplatin on Biological Characteristics of Human Hepatic Cancer Cells HepG2

OBJECTIVE To investigate the effect of lovastatin separately or in combination with cisplatin on biological characteristics of human hepatic cancer cells HepG2 and to explore the molecular mechanisms. METHODS After 48 h of treatment cells with different concentrations of lovastatin and lovastatin combined with cisplatin, the proliferation inhibitory effect on HepG2 cells was assessed by CCK-8 assay. Jin's Q value was adopted to judge the efficacy of the joint-medicinal application. The long-term effects of drugs on hepatoma cells was studied by plate cloning test. The motile ability was detected by wound healing test and invasion ability was determined by Transwell assay. The cell cycle changes and apoptotic ratio was detected by flow cytometry. The expression of Bcl-2, Bax, and caspase-3 was examined with Western blotting. RESULTS Lovastatin inhibited the proliferation of HepG2 cells in a concentration-dependent manner. The results of Jin's Q value showed that lovastatin could enhance the anti-tumor effect of cisplatin. Plate cloning test showed that lovastatin could significantly inhibit HepG2 cells clone formation rate. Wound healing assay showed that lovastatin can significantly reduce the mobility of hepatocellular carcinoma cells. Transwell cell invasion test showed that lovastatin significantly reduced the number of perforating cells. The flow cytometry showed that lovastatin caused cell cycle arrest at G₀/G₁ phase with the reduction of S phase cell, the apoptotic ratio was increased by lovastatin. Western blotting assay confirmed that lovastatin could decrease the expression of Bcl-2, and increase the expression of Bax and caspase-3. CONCLUSION Lovastatin can inhibit the ability of proliferation, migration and invasion of HepG2 cells. The combination of lovastatin and cisplatin can enhance the anti-tumor effect of cisplatin in vitro. The mechanisms may be induce apoptosis through mitochondrial pathway.