Affiliation:
1. Department of Obstetrics and Gynecology, Nanjing Maternity and Child Health Care Hospital, Women’s Hospital of Nanjing Medical University, 123 Mochou Rd, Nanjing, Jiangsu 210004, China
Abstract
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
20 articles.
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