The Function And Clinical Significance Of USP11 And XIAP On Drug Resistance Of Ovarian Cancer

Ovarian cancer is a female reproductive system malignancy,and it is also the highest mortality rate of gynecologic tumors.The 5-year survival rate is only 35%.Carboplatin is the first line of treatment for ovarian cancer.The study found that patients who are sensitive to carboplatin chemotherapy have a better prognosis,but many patients may experience insensitivity to the effects of carboplatin chemotherapy.Therefore,to clarify the mechanism of carboplatin-resistant drug resistance in patients with ovarian cancer and to improve the patient’s chemosensitivity to carboplatin is an urgent problem and key to the treatment of ovarian cancer.XIAP is an important member of the anti-apoptotic protein family,which has the function of resistance to apoptosis.In ovarian cancer cell lines ES2 and 3AO,when the expression of XIAP was decreased,cell proliferation was inhibited,and apoptosis was significantly increased.In cell proliferation and apoptosis experiments,carboplatin was added to culture ovarian cancer cells and cells with low expression of XIAP were found to have increased sensitivity to carboplatin.Further experiments showed that XIAP promoted carboplatin-induced apoptosis by increasing cleaved Caspase3,Caspase9 and PARP.To explore the clinical significance of XIAP,the expression of XIAP in 151 ovarian cancer tissue microarrays was detected by immunohistochemistry.The results showed that most patients with high expression of XIAP were resistant to carboplatin and presented poor prognosis.USP11 is a member of the deubiquitinating enzyme family and plays an important role in a variety of tumors.Changed the expression of USP11 in ovarian cancer cells,cell proliferation and apoptosis experiments were carried out with carboplatin culture cells.It is found that USP11 plays an oncogene function in ovarian cancer and is closely related to carboplatin sensitivity.Ovarian cancer cells with low expression of USP11 promoted carboplatin-induced apoptosis by increasing cleaved Caspase3,Caspase9 and PARP.Tumor formation experiments in nude mice also showed that mice with low expression of USP11 cells were more sensitive to carboplatin and the ability of tumor formation in mice were lower than that in the control group.The expression of USP11 in 151 cases of ovarian cancer tissue microarrays was detected.And analysis showed that USP11 expression was related to prognosis and carboplatin sensitivity.To find out the mechanism by which USP11 functions,immunoprecipitation-mass spectrometry experiments were performed to identify a series of molecules that interact with USP11 in ovarian cancer.Through literature screening,it was speculated five moleules,respectively are HSPA5,HSPA1 A,TGM2,PRMT5 and DDX5,these may serve as downstream molecules of USP11.USP11 increases the sensitivity to carboplatin and inhibits tumor proliferation by stabilizing the expression of downstream proteins.In summary,USP11 and XIAP play a role in promoting tumor growth in ovarian cancer,and reveal the close relationship between the expression of two molecules and carboplatin sensitivity.Decreasing the expression of USP11 and XIAP can increase the sensitivity of carboplatin and promote apoptosis,providing a new direction for the treatment of ovarian cancer.