RAPAMYCIN SELECTIVELY INHIBITS THE GROWTH OF CHILDHOOD RHABDOMYOSARCOMA CELLS THROUGH INHIBITION OF SIGNALING VIA THE TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTOR

We show that cell lines derived from childhood alveolar rhabdomyosarco ma (RMS) are very sensitive to the growth-inhibitory effects of the im munosuppressive agent rapamycin (RAP), compared to other human cell li nes (50% inhibitory concentration range of 0.1-8 ng/ml, compared to 12 80 to > 10,000 ng/ml). Our data suggest that the sensitivity of RMS li nes is due to RAP inhibition of insulin-like growth factor 1 receptor- mediated signaling, which is essential for continued proliferation of RMS cells. The embryonal RMS line Rh1, which was resistant to RAP in s erum-containing medium (50% inhibitory concentration, 4180 ng/ml), was highly sensitive under autocrine conditions of growth, indicating tha t resistance was due to paracrine signaling pathways insensitive to RA P action. FK506 reversed RAP action in all cell lines, indicating a de pendence on complexing with the cytosolic FK506-binding protein for ac tivity.