Lobaplatin induces pyroptosis in cervical cancer cells via caspase-3/GSDME pathway.

Background Increasing evidence shows that GSDME is involved in tumor chemotherapy. Lobaplatin is an important chemotherapy drug for the treatment of cervical cancer. However, the exact mechanism of lobaplatin in the treatment of cervical cancer remains unclear. Objective In this study, we study whether GSDME is a new mechanism of lobaplatin in the treatment of cervical cancer. Methods Cell pyroptosis was measured by Cell Counting Kit-8 and flow cytometry analyses. Western blot analysis was used to check proteins expression. Results The cell viability was significantly decreased by lobaplatin treatment. Compared with the control group, the percentage of pyroptosis (PI and Annexin-V double-positive cells) increased after lobaplatin treatment. In addition, lobaplatin induced caspase-3 activation and GSDME cleavage. z-DEVD, a specific inhibitor of caspase-3, reduced lobaplatin-mediated GSDME cleavage and concurrently inhibited pyroptosis. More importantly, GSDME deficiency obviously reduced lobaplatin-induced pyroptosis. Conclusion These data demonstrated that caspase-3/GSDME axis contributed to the lobaplatin-mediated pyroptosis in cervical cancer cells. This finding indicates that GSDME-mediated pyroptosis is a new mechanism for lobaplatin to kill tumor cells and suggest that caspase-3/GSDME pathway offer new insights into cancer chemotherapy.