Reversal Effects of 20(R)- and 20(S)-Ginsenoside-Rg3 on Daunorubicin Uptake in Multidrug-Resistant Leukemia Cells...

Multidrug resistance (MDR), frequently mediated by overexpression of the P-glycoprotein (P-gp) efflux transporter, remains a major challenge in the treatment of leukemia by limiting intracellular accumulation of chemotherapeutic agents such as daunorubicin (DNR). This study evaluates the applicability of a microfluidic-based single-cell biochip to investigate the reversal effects of microgram-level ginsenosides on daunorubicin uptake in multidrug-resistant leukemia cells. Pure ginsenosides are difficult to obtain in bulk and are typically available only in milligram quantities, which restricts their evaluation using conventional MDR assays such as flow cytometry that require large cell populations and substantial amounts of compounds. To address this limitation, a microfluidic single-cell biochip (SCB) requiring microgram quantities of ginsenosides (<100 µg) and fewer than ten cells was employed. Intracellular DNR accumulation was measured in the CEM/VLB1000 leukemia cell line following treatment with DNR alone or in combination with ginsenoside Rg3-R, ginsenoside Rg3-S, 20(S)-protopanaxatriol (PPT), and 20(S)-protopanaxadiol (PPD), in order to compare their relative efficacy in enhancing drug accumulation. Although Rg3-R and Rg3-S share highly similar chemical structures and are glycosylated derivatives of the PPD aglycone, Rg3-S exhibited greater potency in increasing intracellular daunorubicin accumulation than Rg3-R, and both were more effective than PPD. These findings underscore the importance of ginsenoside stereochemistry modulating P-gp-associated drug resistance and demonstrate the utility of the SCB platform for quantifying daunorubicin accumulation in multidrug-resistant leukemia cells at single-cell resolution.