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. The cell line RD, derived from an embryonic rhabdomyosarcoma tumor, was used as an in vitro model to examine the development of drug resistance. A cell line resistant to actinomycin D (RD-DAC) was developed by growing RD in increasing concentrations of the drug. The ID50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant line to actinomycin D was more than 15 times that of the parental line. The resistant line was cross-resistant to vincristine and doxorubicin. Resistance to actinomycin D resulted in increased P-glycoprotein expression, which was associated with a change in desmin and vimentin expression. These results suggest that exposure to chemotherapeutic drugs can induce not only classical multidrug resistance, but also a process of cellular differentiation in rhabdomyosarcoma cells.
Melguizo
C
C
Department of Morphological Sciences, School of Medicine, University of Granada, Spain.
Prados
J
J
Fernández
J E
JE
Vélez
C
C
Alvarez
L
L
Aránega
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division; D004247:DNA / Q000032:analysis; D003609:Dactinomycin / Q000494:pharmacology*; D003893:Desmin / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D012208:Rhabdomyosarcoma; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D003893:Desmin; D008562:Membrane Glycoproteins; D014746:Vimentin; D003609:Dactinomycin; D004247:DNA