Cisplatin promotes pyroptosis of gastric cancer cells by activating GSDME

Abstract

ABSTRACTAccording to studies, numerous chemotherapeutic drugs can facilitate programmed cell death via pyroptosis. Clarifying the mechanism by which cisplatin kills gastric cancer cells is crucial for enhancing gastric cancer’s sensitivity to chemotherapy and elucidating the mechanism of drug resistance in gastric cancer. The differentially expressed genes following cisplatin treatment were identified using second-generation sequencing technology. Bioinformatics was used to investigate the functional enrichment of differentially expressed genes and core genes in tumor cells killed by cisplatin. Cox regression analyses were used to examine the pyroptosis core genes that worked as independent prognostic factors for patients with gastric cancer. The expression of core genes in gastric cancer cells was silenced by siRNA, and the changes in the proliferation of gastric cancer cells were observed. The expression of related genes and the survival of gastric cancer cells after the addition of cisplatin were observed. The second-generation sequencing, RT-PCR and Western blotting showed that the pyroptosis core gene was significantly highly expressed after cisplatin treatment. The results of differential gene enrichment of cisplatin-treated gastric cancer cells showed that differential genes were mainly concentrated in biological processes and signaling pathways related to pyroptosis. GSDME protein is highly expressed after cisplatin treatment, and it is also a poor prognostic factor for gastric cancer patients and an independent prognostic factor. After the same dose of cisplatin treatment, the survival rate of siGSDME gastric cancer cells was significantly higher than that of GSDME regular expression gastric cancer cells. After acting on gastric cancer cells, cisplatin triggers pyroptosis by stimulating the activation of genes such as GSDME, resulting in the death of gastric cancer cells. GSDME is an independent prognostic factor for gastric cancer patients and is significantly linked with a shorter OS. In gastric cancer cells, silencing GSDME can substantially reduce cisplatin’s cytotoxicity.