Non-steroidal anti-inflammatory drugs induce apoptosis in implanted hepatoma in mice

AIM: To study the mechanism of the effect of NSAIDs on apoptosis in mice hepatoma at anti-inflammatory doses. METHODS: Kunming breed mice were inoculated subcutaneously in the flank with mice hepatoma H22 cell line. The effects of ibuprofen, indomethacin, and nimesulide on apoptosis were determined by using electron microscopy, agarose gel electrophoresis, flow cytometry, and Western blot analysis of the expression of c-myc, bcl-x_L and bcl-2 proteins. RESULTS: NSAIDs induced apoptosis of mice implanted hepatoma, which includes the morphological changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the “ladder pattern revealed by agarose gel electrophoresis of DNA. The apoptotic index was increased to 15.0%±1.0%, 29.7%±1.5%, 46.3%±3.5% from 3.3%±0.6% by detecting Sub-G_1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2 and bcl-x_L were significantly reduced by treatment with nimesulide. Ibuprofen and indomethacin decreased bcl-2 expression but increased bcl-x_L expression. C-myc wasn't changed in these groups. CONCLUSION: These results suggest that NSAIDs induce apoptosis of mice hepatoma, which may be due to their regulation on the expressions of bcl-2 family genes.