Experimental Study On The Effects Of Combination Of The Radioactive Seeds ¹²⁵I And Doxorubicin (ADM) In The Treatment Of Breast Carcinoma

Objective: To investigate the effects of breast carcinoma cells apoptosis induced by the combination of the radioactive seeds ¹²⁵I and ADM, and the effects of ¹²⁵I on the concentration of the ADM in the breast carcinoma cells.Methods: Two strains of the breast carcinoma cells(sensitive strain MCF-7 and drug-resistant strain MCF-7/ADM)were individually and randomly divided into four groups by 2×2 factorial design , there are Control Group, Simple ¹²⁵I seeds Group, Simple ADM Group and ¹²⁵I seeds combined with ADM Group. The irradiation dose of ¹²⁵I was 200cGy, the drug dose of ADM was the IC50 of ADM that whose action time is 48 hours. Cell cycle distribution of MCF-7 and MCF-7/ADM cells were analyzed by Flow cytometry(FCM), and the apoptosis of which were determined by Flow cytometry and Annexin V-FITC staining. Simultaneously to determine the concentration of doxorubicin (ADM) in the both strains breast carcinoma cells of Simple ADM Group and ¹²⁵I combined with ADM Group by high performance liquid chromatography(HPLC).Results: 1. Simplely Low dose rate and continuous irradiation with ¹²⁵I seeds can change cell cycle distribution of MCF-7 and MCF-7/ADM cells cause G2-M phase arrest.And the effect of ¹²⁵I combined with ADM cause G0-G1 phase arrest for the MCF-7 cells, at equal pace following larger proportion apoptosis of cells, but for the MCF-7/ADM cells cell cycle distribution still arrest on G2-M phase.2. Simplely Low dose rate and continuous irradiation with ¹²⁵I seeds can induce apoptosis in the breast carcinoma cells,Flow cytometry and Annexin V staining showed that the earlier period apoptosis rates of MCF-7 cells were 19.22±4.92 %, and of MCF-7/ADM cells which were 11.92±2.74 %. After being treated with ¹²⁵I seeds combined with ADM , the earlier period apoptosis rates of MCF-7 cells oppositely decline,at the same time the rates of advanced period apoptosis and cells necrosis were obviously raise.And For the MCF-7/ADM cells the treatment with ¹²⁵I seeds combined with ADM showed a synergistic effect on the earlier period apoptosis rates .3. A linearity was obtained from 0.025 to 0.5 mg/L of ADM with a correlation coefficient of 0.9999 at the established chromatographic condition. The concentrations of ADM of MCF-7 cells in Simple ADM Group were 0.078±0.005 mg/L,and in ¹²⁵I seeds combined with ADM Group were 0.484±0.016 mg/L, there were significant differences(t=28.546,p < 0.05). For the MCF-7/ADM cells, the concentrations of ADM in Simple ADM Group were 0.458±0.023 mg/L, in ¹²⁵I seeds combined with ADM Group were 0.091±0.007 mg/L,which also had significant difference (t=49.42,p<0.01).Conclusion: 1. Simplely Low dose rate and continuous irradiation with ¹²⁵I seeds can restrain the multiplication of the MCF-7 and MCF-7/ADM cells, which mainly cause G2-M phase arrest.2.Treatment with ¹²⁵I seeds and ADM both can induce apoptosis in the breast carcinoma cells,the combination of them show a synergistic effect.3.The combination of the ¹²⁵I and ADM can increase the concentration of ADM in the sensitive strain MCF-7 to achieve the better therapeutic efficacy. But there is no the same effect for the drug-resistant strain MCF-7/ADM.