ACTINOMYCIN-D TREATMENT LEADS TO DIFFERENTIATION AND INHIBITS PROLIFERATION IN RHABDOMYOSARCOMA CELLS

Human embryonal cell line RD is derived from rhabdomyosarcoma, a tumor of childhood that arises from rhabdomyoblasts probably arrested somew here along their pathway to maturation. Because actinomycin D is a dru g of choice in the treatment of rhabdomyosarcomas, and because it has been used to induce differentiation as an alternative therapy for myel oproliferative syndromes, we treated RD cells with different concentra tions of actinomycin D and evaluated the effects on growth and differe ntiation. Actinomycin D treatment in vitro caused time- and dose-depen dent growth inhibition, interestingly, RD cells treated with Bow close s (2.85 and 5.7 nmol/L) of actinomycin D for 6 days showed morphologic and phenotypic differentiation, with increased expression of desmin, alpha-actinin, and tropomyosin. However, treatment with 11.4 nmol/L ac tinomycin D strongly Inhibited growth and had cytotoxic effects that p revented the cells from attaining myogenic differentiation, We conclud e that exposure of this human embryonal rhabdomyosarcoma cell line to low concentrations of actinomycin D released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. We suggest a potential role for differentiation therapy in the treatm ent of rhabdomyosarcomas.