Characterization of Low-and High-level Adriamycin-Resistant Human Gastric Cancer Cell Lines: Flow Cytometric Studies and Reversal Effect of Verapamil
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We have established two adriamycin (ADM)-resistant sublines with different levels of drug resistance, MKN45R0.05 and MKN45R0.8,from the parental MKN45 human gastric cancer cell line by exposure to stepwise increases in ADM. MKN45R0.05 and MKN45R0.8 cells were 4.8-and 15-fold more resistant to ADM than MKN45 cells, respectively. Flow cytometric (FCM) analysis revealed that MKN45R0.8 cells had significantly lower accumulation of cells in G_2M phase and higher efflux rate of intracellular ADM content than MKN45 and MKN45R0.05 cells. There was no significant increase of P-glycoprotein expression in both resistant sublines by FCM analysis. Verapamil (VPM) showed stronger modifying effects on ADM sensitivity and cell kinetics in MKN45R0.8 than MKN45R0.05 cells. These results indicate that FCM analysis is useful for determining the level of drug resistance, drug accumulation and P-glycoprotein expression in cancer cells, and that the differential resistance-modifying activity of VPM depends on the level of drug resistance.