Reversal Of Multidrug Resistance In Human Breast Cancer MCF-7/ADM Cells By Oxymatrine

Objective:To investigate the effects and mechanism of Oxymatrine,one nature bio active element extract from the natural medicinal herbs,in reversing multidrug resistance (MDR) in the MCF7/ADM cell line.Methods:1. MTT colorimetry was used to detect the inhibition ratio under different concentration of Oxymatrine in MCF-7/ADM and MCF-7/S cell line,then determine the non-cytotoxic and experiment concentration.2. To convincing the Multidrug Resistance of MCF-7/ADM cell line,MTT colorimetry was applied to detect the half-maximal inhibitory concentration (IC50) value of ADM, VCR and Taxol in MCF-7/ADM and MCF-7/S cell line.3. To evaluate the reversal effect of Oxymatrine,MTT colorimetry was employed to detect the half-maximal inhibitory concentration (IC50) value of ADM,VCR and Taxol in MCF-7/ADM and MCF-7/S cell line after the addition of Oxymatrine.4. Flow cytometry was employed to measure P-glycoprotein(P-gP) on the membranes and the intracellular fluorescence intensity of ADM in MCF-7/ADM cell line before and after the addition of Oxymatrine.Results:1. Oxymatrine with concentration lower than 0.75mg/ml had no apparent cytotoxic effects on MCF-7/ADM cell line.2. The half-maximal inhibitory concentration (IC50) value of ADM in MCF-7/S and MCF-7/ADM cell lines are respectively 0.68μg/ml and 51.57μg/ml,the latter was about 75.84-fold to the former. After the treatment of Oxymatrine the IC50 value of ADM in MCF-7/ADM cell line significantly decreased to 8.36μg/ml,the reversal effect is round to 6.26 times;The IC50 value of VCR in MCF-7/S and MCF-7/ADM cell lines are respectively 0.29μg/ml and 11.38μg/ml, the latter was about 39.24-fold to the former. After the treatment of Oxymatrine the IC50 value of ADM in MCF-7/ADM cell line significantly decreased to 0.98μg/ml,the reversal effect is round to 12.44 times;The IC50 value of Taxol in MCF-7/S and MCF-7/ADM cell lines are respectively 0.19μg/ml and 6.45μg/ml,the latter was about 33.95-fold to the former. After the treatment of Oxymatrine the IC50 of ADM in MCF-7/ADM cell line significantly decreased to 0.63μg/ml,the reversal effect is round to 10.90 times. 3. After addition the Oxymatrine at 0.75mg/ml concentration,the concentration of intracellular ADM increased by 2-4 fold. The fluorescent intensity of P-gP on the membrane before and after the addition of Oxymatrine are respectively 39.987±0.693 and 20.016±0.318, the difference is statistically significant (P<0.05).