The Preliminary Study About The Relationship Between The Annexin A1Protein And Paclitaxel Resistence In Ovarian Cancer

Objective:To explore the relationship between the expression of ANXA1protein and ovarian cancer paclitaxel resistance through detecting the expression differences of Annexin A1protein (ANXA1) in ovarian cancer paclitaxel resistance and sensitive cell lines and tissue samples. In order to look for biochemical index to predict the ovarian cancer paclitaxel chemotherapy resistance and provide theoretical and experimental evidence for reversing ovarian cancer paclitaxel resistance in clinic.Methods:1. MTT method was used to detect the Taxol half inhibitory concentration (IC50) and resistance index (RI) of ovarian cancer paclitaxel sensitive cell line (SKOV3) and resistance cell line (SKOV3/Taxol-25).2. Dozens of differentially expressed proteins were filtered out in our group’s former results, which was on the basis of proteomics technology compares protein expression profiling between SKOV3/Taxol-25and SKOV3, ANXA1protein lowly expressed in ovarian cancer paclitaxel resistant cell line was selected as purpose protein which maybe related with ovarian cancer paclitaxel resistance. Western blot and Real Time-PCR(RT-PCR) were used to confirm the expression of ANXA1in protein and mRNA level in pacitaxel resistance and sensitive cell lines.3. The expression differences of ANXA1protein in the tissue specimens of20patiens of ovarian cancer paclitaxel resistance and22 patients of ovarian cancer paclitaxel sensitive were detected by using the immunhistochemical method and the relationship between ANXA1protein and clinical pathological characteristics of ovarian cancer were analyzed.Results:1. The result of MTT showed that the drug resistance of SKOV3/Taxol-25cell line was good, the cell line can used to the follow-up experiments.2. WB and RT-PCR results revealed that the expression of ANXA1protein and mRNA in SKOV3/Taxol-25were significantly lower than that in SKOV3(P<0.05).3. Immunohistochemical result showed that ANXA1protein expression positive rate in paclitaxel resistant group (70%) was lower than that in the sensitive group (95%), the difference was statistically significant(P<0.05). The expression of ANXA1protein was not related to the pathologic classification and histological grade of ovarian cancer(p>0.05), while relating to the clinical stage(P<0.05). The ANXA1protein was not related to the chemosensitivity of low differentiation ovarian cancer [the positive rate of resistance is72.7%(8/11) with the sensitive is93.3%(3/4)].Conclusions:1. The expresion of ANXA1protein in ovarian cancer paclitaxel resistance cell line and tissue samples were significantly lower than that in the sensitive cell line and tissue samples, which prompting the expression of ANXA1protein may associate with the ovarian cancer paclitaxel resistance and maybe a valuable prognostic factor for paclitaxel sensitivity of ovarian cancer patients. 2. The expression of ANXA1protein was related to the clinical stage of ovarian cancer, as the increasing of clinical stage, AnnexinA1downregulated, which suggesting that the downregulating of AnnexinA1protein may promote the invasion and metastasis of ovarian cancer cells.