IASPP Regulation Drug Resistance In Bladder Cancers

Chemotherapy tolerance is one of the important reasons that affect the poor prognosis of cancer patients.As a typical solid tumor,bladder cancer has high tolerance to various chemotherapy drugs.Therefore,it is very important to understand the molecular mechanism of chemotherapy tolerance in bladder cancer.Abnormality of tumor cell apoptosis regulation pathway is one of the im portant methods to prevent the effect of chemotherapy drug induced killing.The apoptosis of tumor cells is regulated by many factors,p53 is an important regulatory factor that affects the regulation of apoptosis of tumor cells.p53 regulates the expressi on of target genes through the regulation of apoptosis and thus affects the apoptosis of tumor cells.However,p53 is influenced by many regulatory factors in the cell.Among them,iASPP is an important inhibitor of p53,and iASPP binds to and inhibits the transcriptional activation of downstream antioxidant target genes by p53,which in turn inhibits apoptosis of tumor cells,thus exerting the role of proto-oncogenes.iASPP belongs to the ASPPs protein family,a large number of studies have shown that iASPP is highly expressed in many kinds of tumors,and is related to tumor chemotherapy tolerance,but the molecular mechanism of iASPP regulating tumor chemotherapy tolerance is not deep enough.In addition,the expression level and role of iASPP in bladder cancer are unknown and remains to be discovered.In this study,real-time quantitative PCR,immunohistochemistry,and immunoblotting were used to confirm that both iASPP m RNA and protein levels were significantly elevated in bladder cancer tissues and cells.After the cell viability was examined in this article,the chemotherapy tolerance of bladder cancer cells was found to be related to iASPP.Through exogenous overexpression and RNAi interference technology,it was confirmed that iASPP interfered with decreased cell resistance,and iASPP overexpression increased cellular drug resistance.In this study,cell flow analysis and real-time quantitative PCR were used to study the mechanism of iASPP enhancing the resistance of bladder cancer cells.The results showed that iASPP can inhibit apoptosis by inhibiting ROS levels.It was also found that iASPP inhibited the expression of Bax m RNA.Promote the expression of anti-apoptosis gene Bcl-2 m RNA.Further through nucleoplasm fraction isolation experiments,it was found that iASPP is mainly located in the cytoplasm,and that these bladder cancer cells undergo functional inhibitory mutations in p53.In order to further clarify the molecular mechanism of iASPP regulating apoptosis of bladder cancer cells,this study d etected by real-time quantitative PCR and immunoblotting that iASPP increased Nrf2 protein levels and its downstream antioxidant target gene expression(FTH1,HMO1,NQO1),but Nrf2 m RNA and Keap1 protein levels had no effect.In summary,this study demonstrated that iASPP is highly expressed in bladder cancer and may increase the expression of Nrf2 protein,Nrf2 anti-oxidation target gene and proapoptotic Bax in a p53-independent manner,and inhibit the expression of apoptosis inhibitory factor Bcl-2.Inhibits ROS levels,inhibits apoptosis,and enhances the tolerance of bladder cancer cells to various chemotherapeutic drugs.This study will provide new ideas for the study of drug resistance mechanisms in bladder cancer.