Abstract
Multidrug resistance has been a major problem in cancer chemotherapy. In this study, in vitro and in vivo modulations of MDR by ginsenoside Rg 3, a red ginseng saponin, were investigated. In flow cytometric analysis using rhodamine 123 as an artificial substrate, Rg 3 promoted accumulation of rhodamine 123 in drug-resistant KBV20C cells in a dose-dependent manner, but it had no effect on parental KB cells. Additionally Rg 3 inhibited [ 3 H ]vinblastine efflux and reversed MDR to doxorubicin, COL, VCR, and VP-16 in KBV20C cells. Reverse transcriptase-polymerase chain reaction and immuno-blot analysis after exposure of KBV20C cells to Rg 3 showed that inhibition of drug efflux by Rg 3 was due to neither repression of MDR1 gene expression nor Pgp level. Photo-affinity labeling study with [ 3 H ]azidopine, however, revealed that Rg 3 competed with [ 3 H ]azidopine for binding to the Pgp demonstrating that Rg 3 competed with anticancer drug for binding to Pgp thereby blocking drug efflux. Furthermore, Rg 3 increased life span in mice implanted with DOX-resistant murine leukemia P388 cells in vivo and inhibited body weight increase significantly.
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