Multidrug Resistance Phenotype in the RMS-GR Human Rhabdomyosarcoma Cell Line Obtained after Polychemotherapy

Classical cytotoxic treatment of rhabdomyosarcoma (RMS), the most common soft tissue malignancy in children, is often accompanied by significant morbidity and poor response. Chemotherapy may induce multidrug resistance (MDR) associated with the expression of P-glycoprotein, a drug efflux pump which modifies the sensitivity of tumoral cells to drugs. To analyze MDR in RMS we used the RMS-GR cell line, obtained from an embryonal rhabdomyosarcoma treated in vivo with polychemotherapy. The RMS-GR cells showed cross-resistance to vincristine, doxorubicin and actinomycin D, the drugs of choice in the conventional treatment of RMS. Polymerase chain reaction (PCR) analysis showed that these RMS cells overexpressed mdr1 /P-glycoprotein. The pattern of resistance and the level of P-glycoprotein expression were similar to those found in the resistant RMS TE.32.7.DAC cell line obtained in vitro . Southern blot analysis showed that mdr1 overexpression was not due to amplification of the gene. Our results showed that the in vivo treatment of embryonal RMS may induce an MDR phenotype mediated by mdr1 /P-glycoprotein in RMS cells.