Effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells

AIM:To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. METHODS:Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique.The growth and the invasiveness of GBC-SD cells in vitro were evaluated by the tetrazolium-based colorimetric assay and by the Matrigel experiment and the crossing-river test.Expression of PCNA, Ki-67, MMP 2 and TIMP 2 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. RESULTS:In vitro norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose-and time-dependent manner, with the IC 50 value of 56.18 g/mL at 48 h.Norcantharidin began to inhibit the invasion of GBC-SD cells at the concentration of 5 g/mL, and the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly at 40 g/mL.After treatment with norcantharidin, the expression of PCNA, Ki-67, and MMP 2 was significantly decreased.With the increase in TIMP 2 expression, the MMP 2 to TIMP 2 ratio was decreased significantly (P<0.05). CONCLUSION:Norcantharidin inhibits the proliferation and growth of human gallbladder carcinoma cells in vitro at relatively low concentrations by inhibiting PCNA and Ki-67 expression.Its anti-invasive activity may be the result of decrease in MMP 2 to TIMP 2 ratio and reduced cell motility.