| Background and Objective:Endometrial cancer is primary epithelial malignant tumor and one of the most common female genital cancers. Its incidence is increasing year by year. The treatment of endometrial cancer depends on surgery, adjuvant chemotherapy and radiotherapy at present. Chemotherapy is mainly used for advanced and recurrent cases. In the present period, cytotoxic drugs are the essential drugs in chemotherapy. However, the serious side-effects can not be ignored, to seek new alternative treatments become a research hotspot. There is close relationship between PPARy(peroxisome proliferators-activated receptor gamma)and fat metabolism,insulin resistance. Endometrial cancer, the malignant tumor with obvious characteristics, is also closely related to obesity, hypertension, diabetes mellitus and high insulin level. It is suggested that PPARy be relative to development and growth of endometrial cancer. Several studies have indicated that PPARy's agonist could induce apoptosis of tumor cells in vitro test, but they couldn't obtain the corresponding results in vivo tests and clinical trials.In our study, we established the transplanted tumor model of human endometrial cancer in BALB/c-nu mice with KLE cells.The objective is to investigate the synergistic effects of ROZ and DDP on the growth of them.Methods:KLE cells were transplanted into nude mice to form study model. KLE cells were cultured at 37℃,5% CO2 humid conditions. The culture medium was DMEM with 10% FBS. They were digested by 0.25% trypsin. A single cell suspension of KLE cells in PBS with the concentration of 1.0×108/ml was prepared for injecting. The percentage of viable cells was 98% as determined by trypan blue staining. The 0.1 ml cells were injected into subcutaneous tissue of nude mice under the aseptic condition. They were raised at the aseptic constant temperature, constant humidity environment and were observed every day. Careful observation on general conditions is necessary for nude mice. The volumes of the transplanted tumors were obtained by measuring diameter.When the models were established (subcutaneous nodules≥200mm3), they were randomly divided into 6 groups:A(controlgroup),B(DDP 1 mg/kg),C(DDP3mg/kg),D(ROZ50mg/kg),E(DDP1mg/kg+R OZ50mg/kg), F(DDP3mg/kg+ROZ50mg/kg). DDP was given by intraperitoneal injection every two days, ROZ intragastric administration every day. During the period of observation, the volumes of the transplanted tumors were measured every 4 days. The tumor growth inhibiting rates of each group were calculated. Moreover the curves of BALB\c-nu mice growth were drawn. On the 38th days of the experiment, BALB\c-nu mice were euthanized and xenograft tumors were measured. Hoechst staining was used and apoptosis of KLE cells was observed by fluorescence microscope. The expression of NF-κB and PTEN protein in subcutaneous tumors were determined by immunohistochemical method with image analysis system. Experimental date was statistically analyzed by One Way ANOVA.Results:Tumor formation rate of KLE cells in nude mice was 97.4%.The general conditions of mice with tumor was good and there was not obviously ulcerate, on the surface of tumor bodies.Significant differences in tumor inhibiting rates were found between the treatment groups and the control group(P<0.05).The tumor inhibitory rate of B,C,D,E,F 5 group was24.41%,43.34%,49.67%,78.02%,84.78%, respectively, and the combination group showed synergic effect on inhibiting the growth of the xenografts with a q value of 1.19. Contrary to control group, the expression of subcutaneous tumor NF-κB was down-regulated and PTEN was obviously up-regulated by rosiglitazone and its combination with cisplatin.Conclusion:KLE cells have good tumorgenic ability in nude mice. Rosiglitazone could enhance inhibition of the growth of endometrial tumor by combination with cisplatin. Its mechanism might be related to up-regulated expression of PTEN and down-regulated expression of NF-κB. |
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