Studies On The Relationship Between STC1 And The Ovarian Cancer And The Influence Of The Drug TSA On Its Biological Behavior

Ovarian cancer is one of common gynecologic malignancy with the characteristics of difficult to discover in the early state,easy to metastasize and poor prognosis, so its mortality rate is in the first palce. However, the cause is still not very clear, the incidence may be related to age,birth,blood type,mental factors,the environment and so on.Stanniocalcin1(STC1) is a glycoprotein hormone,playing the paracrine or autocrine role in the variety of physiological functions of the body.It was reported that STC1 also plays an important role in the development and the process of human tumor,But there are few reports about the relationship of STC1 and ovarian tumorigenesis development at home and abroad.TSA is a histone acetyl enzyme inhibitors(HDACIs),in vitro,it could inhibit proliferation and induce apoptosis and differentiation for a variety of tumor cell lines.This experiment study the relationship of STC1 and the development of ovarian cancer,and also study the influence of STC1 expression after using TSA.Thus it can provide a new target and the possible mechanism for the ovarian cancer gene therapy .Objectives:(1) To study whether the expression of STC1 in ovarian tumor tissues and its clinical significance,to determine whether the potential molecular target of the treatment of ovarian cancer;(2) To detect the expression of ovarian cancer cell A2780/Taxol in STC1,then it can provide further researching mechanism;(3) To investigate the biological effects of ovarian cancer cell lines of the A2780 and A2780/Taxol after using TSA, study the feasibility as a potential treatment of ovarian cancer and in the resistance.Methods:(1) Using immunohistochemistry SP staining method examine the expressions of STC1 in 16 cases of normal ovaries,18 ovarian benign tumors,15 cases of borderline and malignant tumors,53 canses of ovarian cancers.They are analyzed by Chi-square test of SPSS17.0;(2) Using cell immunohistochemistry ,RT-polymerase chain reaction and western blotting examine the expressions of STC1 in ovarian carcinoma cell line A2780,A2780/Taxol and after using TSA;(3) Using flow cytometry examine the expression of STC1 and the change of cell cycle in ovarian carcinoma cell lines A2780,A2780/Taxol.Results:(1) STC1 in normal ovarian tissue,ovarian benign tumor,borderline ovarian tumors,ovarian cancer,interstitial cells were expressed.In stromal cells ,from normal ovarian tissue,ovarian benign tumor,borderline ovarian tumors to ovarian cancer, STC1 expression decreased gradually, were 93.8%(15/16), 88.9% (16/18), 80.0%(12/15), 48.3%(28/58). There was significant difference between them.(P<0.05).(2) The expression level of STC1 in borderline malignancy epithelial cells was significantly lower than those in ovarian carcinoma (P<0.05),The expression of STC1 protein in ovarian carcinoma showed negatively relationship with the histological differentiation, clinical stage and lymphatic metastasis(P>0.05), and was positively correlated with the histological classification(P<0.05).(3) The expression of STC1 could be examined in all two ovarian carcinoma cell lines by cell immuohistochemistry ,RT-ploymerase chain reaction and western blotting.The expression of STC1 is down after using TSA in all two ovarian carcinoma.(4) Flow cytometry revealed that the role of drμgs after TSA in two kinds of expression in ovarian cancer cell lines were down.The inhibition role of cancer cells of TSA cause the cell arrest at G1/G2 phase,with S phase cells decreased.Conclusion:(1) The expression of STC1 decreased in the ovary of the cancer process of interstitial,gradually increased in ovarian cancer cells,then determined that it was related with the occurrence and development of ovarian cancer,which may be the potential molecular target for therapy.(2) The expression of STC1 in ovarian cancers was correlated with histological type,serous adenocarcinoma in a higher expression of mucinous cystadenocarcinoma,to explore the mechanism to provide a thought;(3) STC1 expressed in ovarian cancer cell line A2780 and its resistant A2780/Taxol was not significantly different,and the role of drμg TSA expression decreased and there was no significantly different between the two levels,then indicating the mechanism of STC1 may be unrelated to paclitaxel.TSA may be as the therapy of resistance of ovarian cancer,and it could provide strong evidence for further research on the mechanism of STC1 expression of TSA.(4) The inhibition role of TSA on the A2780 and resistance lines A2780/Taxol is to make cells arrest at G1/G2 phase,to study the mechanism ,it may be the new therapeutic drugs of ovarian cancer,in particular,it may be the new breakthroμgh of ovarian cancer resisitance treatment.