| Objective:The incidence of ovarian cancer is the third in the female reproductive system malignancies, and this trend is rising recently. The mortality is in the first place. Because of ovarian cancer's onset and progress is conceal,70% patients are terminal when discovered with 30% of them have a 5-year survival rate. The main reasons of ovarian cancer too difficult to cure are invasion and metastasis. Many drugs can be used to cure ovarian cancer at present, but the drug resistance to chemotherapy of ovarian cancer patients has become the important influence factor to impact the 5-year survival rate. As2O3 is a traditional Chinese medicine (TCM) has a long history which as a kind of active principle picked up from arsenic trioxide. Arsenic trioxide was approved to cure acute promyelocytic leukemia (APL) by the food and drug administration (FDA) of U.S.A in 2000. Research shows that arsenic trioxide not only has a satisfied curative effect to cure APL, but also can inhibition the invasion and metastasis of many solid tumor. It has a chemical selectivity characteristic, less bone marrow depression effect and no cross resistance with other chemotherapeutics, so more and more research at home and abroad pay close attention to this drug. At the same time, with the development of technique for TCM quality control and researchers know more about it, this drug's clinical value become more significant. The purpose of this study was to examine whether arsenic trioxide has any effect on the invasion and metastasis of ovarian cancer cells and to discuss the mechanism of arsenic trioxide to impact on it, and to guide for the clinical medication.Methods:Chose the human ovarian cancer cell line SKOV3 as the target of this study. Cultured the cell line in vitro and chose the cells which were in exponential growth phase. To set up blank control group and three experimental groups which dealt with three different concentrations of arsenic trioxide(0.5μmol/L,1μmol/L,2μmol/L). The effects of arsenic trioxide on the four groups of ovarian cancer cell line SKOV3 were detected by Transwell assay. The expression level of uPA and uPARmRNA and protein were detected by real-time quantitative PCR and SABC immune-tissue-chemistry method. The data from the experiment was represented by x±s and analyzed by statistics software SPSS 17.0. Student's t test was used to analyze drug treatment groups with blank control group. Single factor analysis of variance was used between the treatment groups. P<0.05 said differences are statistically significant.Results:The count of cells which through the membrane filter of the small room are 152.56±17.36,131.67±10.10,102.11±12.74,63.33±11.37; they are all derived from control group and the three experimental groups which dealt by different concentrations As2O3 respectively. The control group compared with the experimental groups showed that the results were statistically significant difference (P<0.05). The number of the experimental group cells which through the small room was much less with the decrease of As2O3 concentration, and each group had a significant difference when compared with each other (P<0.05). The Real-time quantitative polymerase chain reaction (RT-PCR) showed that the treatment groups, the expression level of uPA and uPARmRNA are all much less than the control group. Binary comparison was statistically significant (P<0.05). The expression of each treatment group showed a significant downward trend with the decrease concentration of As2O3 (P< 0.05). Immune-tissue-chemistry method showed that the positive of uPA was that dyed claybank in the cytolymph, and the positive of uPAR appeared that the cell membrane were dyed to claybank. In the control group, the strong positive expression of uPA and uPAR were visible, and with the experimental drug concentration increased the dyeing became weak gradually in the treatment groups, meanwhile the number of the positive cells reduced. The cytoplasm and cell membrane were not seen tan-yellow dyeing in the negative control group. All the experiments showed that As2O3 could inhibit the expression of uPA and uPAR, and its role was more obvious with the increase of As2O3 concentration.Conclusion:Arsenic trioxide can inhibit the invasion and metastasis of people ovarian cancer cell line SKOV3, The mechanism might be associated with the reduction of uPA and uPAR expression. |
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