Hedgehog signaling inhibitor cyclopamine induces apoptosis by decreasing Gli2 and Bcl2 expression in human salivary pleomorphic adenoma cells.

Pleomorphic adenoma is the most common benign neoplasm of the salivary gland. Few studies are currently available on pleomorphic adenoma cell apoptosis. The aim of this study was to investigate the effect of cyclopamine induction apoptosis in human salivary pleomorphic adenoma (HSPA) cells and the impact on Gli2 and Bcl2 mRNA levels. Cells were quantified and cell morphology was visualized under microscope. Flow cytometry was used to detect the apoptotic rate. Cyclopamine is considered an efficient blocker of the hedgehog (Hh) signaling pathway. Following treatment with 10 μmol/l cyclopamine for 48 h, the number of cells were reduced, and nuclear pycnosis or fragmentation, as well as chromatospherite disfiguration apoptotic morphology were observed under microscope. One-way ANOVA test results revealed a significantly greater decrease (P<0.01) of Gli2 and Bcl2 mRNA levels in the cyclopamine-treated group as compared to the blank control group and dimethyl sulfoxide (DMSO)-treated group. Following treatment with 10 μmol/l cyclopamine for 24 h, the apoptotic rate of the cyclopamine-treated group was significantly higher than that of the blank control and DMSO-treated group (P<0.01). Findings of this study showed that cyclopamine affected the mechanism of HSPA cell apoptosis, which may be associated with the downregulation of Gli2 and Bcl2 mRNA expression levels and the activation of the mitochondrial apoptotic pathways.