| Objective:Ovarian cancer is the third probable cause of cancer-related mortality among women, but it is the leading cause of death from gynecologic cancers. It can not be diagnose in early stage.at the same time.it is easily metastatic witn poor prognosis.The biological mechanism of ovarian cancer is still unclear. Chemotherapy is one of the most important ways for ovarian cancer therapy,and the resistance to anticancer chemotherapeutic drugs.especially to cisplatin which is the first line drug for ovarian cancer, is a main cause which leads to chematherapeutic failure. Thus, to identify the specific molecular that promote chemoresistance is critical in the search for effective therapeutic strategies.Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is the only tumor suppressor gene with the activity of lipid phosphatase and protien phosphatase in present. And it has an important impact on cell growth.proliferation and differentiation, apoptosis,adhesion,migration and blood vessel growth.and many other biological behavior of cells.It was associatd with occurrence and development of neoplasms. To study the expression and alteration of PTENmRNA and protein in ovarian carcinoma cell lines of SKOV3 and SKOV3/DDP in order to comprehend the relationship between the occurrence and development of ovarian cacer and PTEN.Otherwise we analyze the relationship between the growth inhabition of cisplatin-induced and PTEN in order to discuss the relationship of PTEN and the drug resistance of ovarian caicinoma.It will provide new threads prophase diagnosis of neoplasms,develop new drugs to anti-tumor,promote chemoresistance and search target point of gene treatment.Methods:1. MTT assay was used to analyze the curve of growth of SKOV3 and SKOV3/DDP cells,JC50 value of cisplatin,and calculate resistant index.2. To observe the mRNA expression of PTEN in ovarian carcinoma cell lines of SKOV3 and SKOV3/DDP by RT-PCR.3. To observe the protein expression of PTEN in ovarian carcinoma cell lines of SKOV3 and SKOV3/DDP by western blot. 4. MTT assay was used to detect the sensitivity to cisplatin in SKOV3 and SKOV3/DDP cell lines.Results:1. SKOV3 and SKOV3/DDP cells growed adhsively.The multiplicate time of SKOV3 was 34.02 hours and SKOV3/DDP was 43.58.2. Cells were treated with different concentrations of cisplatin for 72 hours, the inhabitory rate increased along with the increasing concentration of cisplatin.and it showed a clear dose-dependent. The inhabitory rate of resistant cell line was significantly lower than that in sensitive cell line (P＜0.05)3. The IC50 to cisplatin of SKOV3 and SKOV3/DDP were 3.4658±0.0990μg/ml,13.4752±1.7803μg/ml respectively.The resistant index was 3.89.which could be used in the test.4. The expression of PTENmRNA in SKOV3 cells were significantly higher than those in SKOV3/DDP cells,which were 0.4470±0.0545 and 0.1995±0.1047 respectively (P＜0.05)5. The expression of PTEN protein in SKOV3 cells were significantly higher than those in SKOV3/DDP cells.which were 0.4528±0.1079 and 0.1882±0.0547 respectively (P<0.05)6.After being effected by cisplatin for 72h,MTT assay showed that the cisplatin resistance increased with the decreasing of PTEN expression. The IC50 to cisplatin was negatively correlated with PTENmRNA (r=-0.760,)P<0.05) and PTEN protein (r=-0.794,P<0.05)Conclusions:PTENmRNA and protein expressed in ovarian cell lines,and the expressions were obviously lower in resistant cell line than in sensitive cell line.The decreasing expression of PTEN was definitely related to the cisplatin resistance of ovarian cancer. |
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