The Expression And Significance Of HIF-1a And XIAP In Human Ovarian Cancer

Objective: The occurrence of tumor is closely related to the cell proliferation andapoptosis. XIAP, one of the strongest factors in inhibiting apoptosis which is found inhuman embryonic brain cells, can inhibit apoptosis by inhibiting the activation of caspase3,6,7,9, and then lead to the occurrence of tumor. Hypoxia is one of the basic characteristicsof solid tumor microenvironment, hypoxia induced factor（HIF）,a transcription factor, iswidely exists in the body and mammal under anoxic conditions. HIF-1a is one of HIFsubunits, its expression and activity determines the biological activity of HIF-1.Experimental studies find that HIF-1a and XIAP have a certain link in the occurrence ofhuman ovarian cancer and resistance, but the specific mechanism is still unclear, but alsovery little research reported. This experiment investigates the expression of HIF-1a andXIAP in normal ovarian tissue, organization of ovarian cancer and ovarian cancer cell lineSKOV3,so that investigate the possible mechanism of XIAP and HIF-1a in human ovariancancer occurrence, and provide possible theoretical basis for the targeted therapy ofovarian cancer.Methods:1.Using immunohistochemical technique (EnVision method) detecting theexpression of XIAP and HIF-1a in10cases of normal ovarian tissue,10cases ofbenign ovarian tumor,10cases of border ovarian tumor and30cases of malignant ovariancancer tissue samples,and discuss the possible mechanism of XIAP and HIF-1a in humanovarian cancer occurrence, and provide possible theory basis for the targeted therapy ofovarian cancer.2. Cultivated people ovarian cancer cell line SKOV3, joined promoter and inhibitor intocell culture bottles of HIF-1a and extracted the total RNA of SKOV3cells, observedexpression change of XIAP and HIF-1a genes by RT-PCR technique.3. All experimental data process analysised by SPSS19.0statistical software.Results:1.The positive expression rate of XIAP in epithelial ovarian cancer、borderlineovarian tumors, and benign ovarian tumors were60%(18/30),70%(7/10) and20%(2/10),and were0%(0/10) in normal ovarian tissue;The positive expression rate of epithelialovarian cancer groups were significantly higher than that of benign ovarian tumor groups,holds a statistically significant difference (P=0.028); the positive expression rate has no obvious difference between epithelial ovarian cancer and borderline ovarian tumors,there isno statistical significance (P=0.85);the positive expression rate between border andbenign ovarian tumor groups have obvious differences,and holds a statistically significantdifference (P=0.025);2. The positive expression rate of HIF-1a in epithelial ovarian cancer、borderline ovariantumors、benign ovarian tumors and normal ovarian tissue were60.3%(19/30),70%(7/10),20%(2/10) and10%(1/10); The result shows: The positive expression rate of epithelialovarian cancer groups were significantly higher than that of benign ovarian tumor groups,holds a statistically significant difference(P=0.044); the positive expression rate has noobvious difference between epithelial ovarian cancer and borderline ovarian tumors,there isno statistical significance(P=1.000); the positive expression rate between border andbenign ovarian tumor groups have obvious differences,and holds a statistically significantdifference(P=0.028); the positive expression rate between epithelial ovarian cancer andborderline ovarian tumors were significantly higher than the normal ovary, holds astatistically significant difference(P values were0.003and0.008).3.The relationship between the positive expression of XIAP、 HIF-1a and clinicalpathological features:the positive expression rate of XIAP and HIF-1a in thelate clinical stage group (stage Ⅲ and Ⅳ) was obviously higher than that of the earlyclinical stage (stage Ⅰ and Ⅱ) group (P=0.007),and has nothing to do with the patients’age、pathological classification and lymph node metastasis (P>0.05).4. The analysis of correlation between HIF-1a and XIAP in epithelial ovarian cancer:XIAPis positively correlated with HIF-1a (r=0.359; P=0.359).5. The results of RT-PCR detection: the expression quantity of HIF-1a mRNA in Ovariancancer cell line SKOV3increased gradually with the extension of oxygen（promoter ofHIF-1a）time, the expression quantity of HIF-1a mRNA arrived peak with24h anoxia andfalled with36h anoxia; with the increase of the amount of HIF-1a mRNA, XIAP mRNAincreased accordingly. The expression of the amount of HIF-1a mRNA reducedsignificantly by adding rapamycin, inhibitor of HIF-1a,and XIAP mRNA diminished withthe amount of HIF-1a expression.Conclusion:1.The expression of HIF-1a and XIAP in primary epithelial ovarian cancertissue is significantly higher than in the benign ovarian tumor tissue, this prompt HIF-1aand XIAP may be involved in the occurrence of ovarian malignant tumors. 2. The expression of HIF-1a and XIAP is associated with clinical stage, and has nothing todo with the patient age、pathological classification and without lymph node metastasis, ahigh expression of HIF-1a and XIAP may be associated with prognosis.3. In hypoxia environment,XIAP mRNA changes with HIF-1a mRNA,and HIF-1a mayhave a regulatory role on XIAP.Maybe, both HIF-1a and XIAP promote the occurrence ofovarian cancer.