Abstract
OBJECTIVE: To assess the inhibitory effect of diltiazem, a calcium channel inhibitor, on the proliferation and mobility of human hepatocellular carcinoma cells in vitro and explore the possible mechanism. METHODS: Two human hepatocellular carcinoma cell lines, MHCC97H and 7402, were treated with different concentrations (0-400 μmol/L) of diltiazem for 12, 24, or 48 h, and the changes in the cell proliferation and mobility were observed with MTT assay and wound healing assay, respectively. The changes in the expressions of calcium-activated chloride channel TMEM16A at mRNA and protein levels in the treated cells were detected using RT-PCR and immunocytochemistry. RESULTS: Treatment with diltiazem obviously inhibited the proliferation and suppressed the mobility of MHCC97H and 7402 cells in a time- and concentration-dependent manner (P < 0.05). Treatment with 100 μmol/L diltiazem for 24 h significantly inhibited the proliferation of MHCC97H cells and down-regulated the mRNA and protein levels of TMEM16A. In 7402 cells, diltiazem treatment at 50 μmol/L for 48 h resulted in the most significant inhibitory effect on the cell proliferation and TMEM16A expressions. CONCLUSIONS: Diltiazem can transiently inhibit the invasion of hepatocellular carcinoma cells in vitro possibly by down-regulating the expression of TMEM16A at both the mRNA and protein levels.