The Effects Of Endostatin And Paclitaxel On The Apoptosis Of Breast Cancer SK-BR-3 Cells

Breast cancer is the most common malignancy in women. Chemotherapy is the most important therapeutic method for breast cancer. However, the chemotherapy effect is not very ideal. In the process of tumor growth, the internal new blood vessel formation has a promoting role on the tumor growth and metastasis. It was found that tumor angiogenesis includes two mechanisms. One is the endothelial cells- dependent mechanism, and another is the endothelial cells- independent vasculogenic mimicry(VM) mechanism, namely non-vascular nutritional pathway.As endogenous angiogenesis inhibitors, Endostatin has specific effect on vascular endothelial cells. It can inhibit the cell growth, migration and apoptosis, thus inhibiting the tumor growth. In recent years, it was found that Endostatin could directly inhibit the tumor growth, and induce tumor cell apoptosis. However, the molecular mechanism was still unclear.Objective: To observe the effect of Endostatin and Paclitaxel on breast cancer SK-BR-3 cells, and explore their relation to the cell apoptosis. To observe the inhibitory effect of Endostatin and Paclitaxel on the VEGF expression of breast cancer SK-BR-3 cells, and explore their relation to the cell apoptosis. To analyze the synergy effects of Paclitaxel and Endostatin combination on breast cancer SK-BR-3 cells.Methods:1 MTT method was used to detect the inhibitory effect of chemotherapy drugs on breast cancer SK-BR-3 cells.2 Western blot method was used to detect the effect of Endostatin and Paclitaxel on VEGF expression of breast cancer SK-BR-3 cells.3 Immunocytochemistry method was used to detect the effect of different drug combinations on the VEGF expression of breast cancer SK-BR-3 cells. Flow cytometry was used to detect the apoptosis of breast cancer SK-BR-3 cells.4 Western blot method was used to detect the apoptosis-related proteins in breast cancer SK-BR-3 cells.Results:1 Paclitaxel has inhibitory effect on the breast cancer SK-BR-3 cells in time and dose dependence manner. The experiment results showed that the IC50 of Paclitaxel on SK-BR-3 cells was 1.08μg/ml. After treatment of Paclitaxel with 1μg/ml for 24 h, the inhibitory rate of SK-BR-3 cells was 33.9%, and the apoptotic rate is 12.4%. After treatment of Paclitaxel with 1μg/ml for 24 h, the expression of Bcl-2 was down-regulated and the Bax expression was up-regulated.2 Endostatin has inhibitory effect on the breast cancer SK-BR-3 cells in time dependence manner. After treatment of Endostatin with 1μg/ml for 24 h, the inhibitory rate of SK-BR-3 cells was 33.7%, and the apoptotic rate is 11.6%. After treatment of Paclitaxel with 1μg/ml for 44 h, the expression of Bcl-2 was down-regulated, but the Bax expression was almost not changed.3 Western blot results showed that both Endostatin and Paclitaxel could reduce the VEGF expression of SK-BR-3 cells. Paclitaxel has more significantly inhibitory effect on VEGF expression(P<0.05).4 The combination of Paclitaxel and Endostatin has significant synergy effects. As compared with Paclitaxel treatment alone, the inhibitory effect of sequential administration was almost not changed. The combination of Paclitaxel and Endostatin has significantly effect on the apoptosis of SK-BR-3 cells, and could reduce the expression of Bcl-2.Conclusions:Both Endostatin and Paclitaxel have inhibitory effect on breast cancer SK-BR-3 cells, and can induce the cell apoptosis. The combination of Endostatin and Paclitaxel has the best inhibitory effect on breast cancer SK-BR- 3 cells, which was probably related to their function on cell apoptosis and VEGF expression.