In Vivo Study Of Indoleamine 2,3-dioxygenase In Ovarian Cancer Chemoresistance

Objective:Establishment of carboplatin-induced drug-resistant ovarian cancer-bearing rat to study their drug resistance.To explore the relationship between indoleamine2,3-dioxygenase(IDO)and drug-resistance in ovarian cancer,detecting the IDO content of drug-resistant ovarian cancer-bearing rats and non-resistant ovarian cancer-bearing rats,respectively.Testing the combined effect of IDO competitive inhibitor1-methyltryptophan(MT-1)and chemotherapy drugs in drug-resistant ovarian cancer tumor-bearing rats.To provide new treatment ideas for the treatment of clinically resistant ovarian cancer.Methods:Fischer344 rats bearing Nu Tu-19 ovarian cancer cell line forms tumor-bearing rat,low-dose,multi-course carboplatin chemotherapy tumor-bearing rats develop drug-resistant tumor-bearing rats.Using non-drug-resistant rats as controls,monitoring tumor growth in drug-resistant tumor-bearing rats and survival of drug-resistant tumor-bearing rats,detecting the drug resistance index of drug-resistant tumor-bearing rats.The rats were sacrificed,and the serum IDO expression was measured by ELISA.Furthermore,MT-1 was injected into the drug-resistant ovarian cancer-bearing rats as the experimental group(MT-1 group),and the drug-resistant ovarian cancer-bearing rats were used as the control group,the serum IDO levels in the two groups of rats were measured.The results were analyzed by SPSS20.0 software: measurement data were expressed as mean ± standard deviation,and the two groups were compared using t test for statistical analysis.P<0.05 was considered statistically significant.Results:1.Drug-resistant ovarian cancer-bearing rats have sparse and loose fur,poor mental state,poor appetite,decreased activity,rapid tumor growth,and increased drug resistance index.2.IDO is related to drug-resistant ovarian cancer-bearing rats.The serum IDO content in drug-resistant ovarian cancer-bearing rats is higher than that in the control group,and the difference is statistically significant(P<0.05).3.The average tumor volume of the drug-resistant ovarian cancer-bearing rats injected with the IDO competitive inhibitor MT-1 group was smaller than that of the drug-resistant ovarian cancer-bearing rats group,and the IDO content was lower than that of the control group.The difference is statistically significant(P<0.05).Conclusion:1.IDO is closely related to drug-resistance of ovarian cancer.It can be used as an indicator of carboplatin resistance in ovarian cancer and provide a predictive indicator of ovarian cancer resistance in clinical.2.IDO competitive inhibitor MT-1 reduces the serum IDO levels of drug-resistant ovarian cancer-bearing rats,increases the sensitivity of drug-resistant ovarian cancer to carboplatin,and provides another idea and method for clinically solving drug resistance of ovarian cancer.