The Mechanism Of Cisplatin Promotes Pyroptosis Of Gastric Cancer Cells By Activating GSDME

Background and Objective:According to previous research,platinum-based chemotherapy drugs trigger programmed cell death in tumor cells via apoptosis.However,as research progresses,an increasing number of programmed cell death mechanisms distinct from apoptosis have been discovered.In recent years,pyroptosis has been discovered as a form of programmed cell death.Numerous chemotherapeutic drugs can facilitate programmed cell death via pyroptosis,according to studies.Clarifying the mechanism by which cisplatin kills gastric cancer cells is crucial for enhancing the sensitivity of gastric cancer to chemotherapy and for elucidating the mechanism of drug resistance in gastric cancer.Materials and Methods:Half inhibitory concentration(IC50)was determined after analyzing the toxicity activity curve of cisplatin-treated gastric cancer cells.The gastric cancer cells were co-cultured for 12 hours with an appropriate amount of cisplatin.Using second-generation sequencing technology,the differentially expressed genes following cisplatin treatment were identified.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.Results and Conclusion:The results of second-generation sequencing,RT-PCR,and Western blotting demonstrated that there was no significant difference in the expression of the majority of apoptosis-related genes in gastric cancer cells treated with cisplatin.In contrast,after cisplatin treatment,the core genes of pyroptosis,including Gasdermin E(GSDME),Gasdermin D(GSDMD),interleukin-6(IL6),and caspase 1(CASP1),were significantly overexpressed.And under a high magnification light microscope,cisplatin’s effect on gastric cancer cells revealed cell membrane rupture and substance efflux.Differential gene enrichment of cisplatin-treated gastric cancer cells revealed that differential genes were mainly concentrated in biological processes and signaling pathways associated with pyroptosis.GSDME protein is significantly expressed after cisplatin treatment,and it is a poor prognostic factor and an independent prognostic factor for patients with gastric cancer.In gastric cancer,hsa-miR-582-5p,hsa-miR-194-5p,LINC00689,MIR29B2 CHG,LIFR-AS1,and HEIH may constitute a ce RNA network associated with GSDME.After receiving the same dose of cisplatin,the survival rate of si GSDME gastric cancer cells was significantly higher than that of GSDME gastric cancer cells with normal expression.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.