ACTINOMYCIN-D CAUSES MULTIDRUG-RESISTANCE AND DIFFERENTIATION IN A HUMAN RHABDOMYOSARCOMA CELL-LINE

The emergence of drug-resistant tumor cells remains a major problem in cancer chemotherapy. Resistance to multiple unrelated antineoplastic drugs may be related, in part, to expression of the P-glycoprotein. Th e cell line RD, derived from an embryonic rhabdomyosarcoma tumor, was used as an in vitro model to examine the development of drug resistanc e. A cell line resistant to actinomycin D (RD-DAC) was developed by gr owing RD in increasing concentrations of the drug. The ID50 (concentra tion of drug needed to induce a 50% reduction in cell growth) of the r esultant line to actinomycin D was more than 15 times that of the pare ntal line. The resistant line was cross-resistant to vincristine and d oxorubicin. Resistance to actinomycin D resulted in increased P-glycop rotein expression, which was associated with a change in desmin and vi mentin expression. These results suggest that exposure to chemotherape utic drugs can induce not only classical multidrug resistance, but als o a process of cellular differentiation in rhabdomyosarcoma cells.