| Background : The mortality of ovarian cancer is the highest in female genital system malignant tumors. The development of the therapeutic effects of traditional operation and radiotherapy at present is not significant, and the increasing of survival rate is not also. So it has been an urgent demand and important research direction of cancer treatment to develop high effect and low toxic anti-tumor drug in current stage.Nordihydroguaiaretic Acid(NDGA), being extracted from Larrea tridentate, can inhibit the growth of multiple tumor cells both in vivo and in vitro. Researchs show that the mechanisms of NDGA inhibiting tumor growth are various, such as inducing apoptosis[1], inducing differenti- ation[2],arresting the cell cycle[3]. Nordy, by artificial improvement of NDGA, possesses high effect and low toxic features. According to our experimental results, Nordy has the same inhibitory effect as NDGA[4].But the mechanisms of Nordy inhibiting tumor growth were undefined yet.In most different histological types of primary epithelial ovarian cancer cells, there is an abnormal high expression of Aurora-A[5]. Aurora-A kinase, as one of the serine threonine kinases, is closely related to centrosome. Aurora-A over expression can cause centrosome over duplication, and then centrosome abnormal division will lead to formation of unipolar spindle, distorted segregation of chromosome and finally form aneuploid, which suggested that Aurora-A may react with ovarian tumor genesis.p53 gene is closely related to tumor genesis and growth, and now the research of it is more sufficiently. Lin Yugeng[6],found that the growth of ovarian cancer cell line SKOV3 with wt-p53 gene transfection was inhibited, which suggested that wt-p53 gene can inhibit growth of tumor cells. And many experiments showed that p53 has a close relation with Aurora-A kinase[7~9].Object: To research the effects of Nordy on expression of Aurora-A and the relationship about expression of between Aurora-A and wt-p53 gene. And to find out the effects of Nordy on growth and cell cycle of ovarian cancer cell line 3AO and SKOV3 and investigate the action mechanism.Method: 1) After being treated with Nordy, the proliferation of 3AO and SKOV3 cells were tested with MTT assay; The effect on cell cycle were analyzed by flow cytometer(FCM).2) After being treated with 25,50,100μmol/L Nordy 72 hours, the expression of Aurora-A and p53 were detected by RT-PCR and Western-blot.3)Statistic analysis: experimental data were shown as mean±s, and analyzed by SPSS11.5 statistic software. Multiple-group analysis chi-square, inter-group analysis SNK-q test. P<0.05 the deference have statistic significance.Results:1) MTT assay shows that after being treated with 25,50,100μmol/L Nordy72 hours, the suppress rates of the two tumor cell strains proliferation were 26.55%, 48.43%, 68.53% in 3AO cell and 22.15%, 45.21%, 66.67% in SKOV3 cell respectively. It suggests that accompany with increment of the Nordy concentration and the prolongation of the action time, the inhibition of the two tumor cell strains proliferation were increasing and showed perfect time-effect relationship and dose- effect relationship. Results of flow cytometry analysis show that after being treated with Nordy 72 hours at different concentrations, the ratio of 3AO cell on G0/G1 phase was increased from 81.36% to 86.96%, the ratio of SKOV3 cell on G0/G1 phase was increased from 73.07% to 79.15%, and the ratio of the two tumor cell strains on S phase were decreased, and on G2/M phase had little change, showing G0/G1 phase blockage.2) Results of RT-PCR and Western-blot show that both in the two tumor cell strains, with the Nordy concentration increasing, expression level of Aurora-A mRNA and protein decreased and expression level of wt-p53 protein increased. 3) The difference, in expression of Aurora-A and p53, is not statistic- cally significant between 3AO and SKOV3 cells.Conclusions: 1) Nordy could inhibit 3AO and SKOV3 cells proliferation , and could block the two tumor cell strains at G0/G1 phase.2) Nordy down regulated expression of Aurora-A mRNA and protein, while expression of wt-p53 protein was up-regulated. The results suggested that by up-regulated the expression of wt-p53, Nordy could inhibit the expression of Aurora-A. And it may be one of the mechanism of tumor growth inhibition.3) The action effect of Nordy on 3AO cell is as same as on SKOV3.4) The result shows that Nordy could inhibit growth of tumor cells through multi-link, such as blocking the cell cycle and inhibiting cytokinin.
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