Journal
CANCER LETTERS
Volume 284, Issue 2, Pages 157-164Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.04.016
Keywords
Alveolar rhabdomyosarcoma; Camptothecin; Differential cytotoxicity; PAX3-FKHR; Apoptosis
Categories
Funding
- NCI NIH HHS [P30CA027165, P30 CA021765, P30 CA021765-30] Funding Source: Medline
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Patients with alveolar rhabdomyosarcoma (ARMS) have poorer response to conventional chemotherapy and lower survival rates than those with embryonal RMS (ERMS). By high-throughput screening, we identified camptothecin as an ARMS-selective inhibitor. Camptothecin more efficiently inhibited proliferation and induced apoptosis in Rh30 (ARMS) than RD (ERMS) cells. Ectopic expression of the PAX3-FKHR (PF) fusion protein in RD cells significantly increased sensitivity, whereas siRNA knockdown of PF decreased sensitivity of Rh30 cells to camptothecin. The sensitization required a transcriptionally active PF, and camptothecin downregulated levels of PF protein. These findings suggest that it is feasible to develop agents that preferentially block the growth of ARMS. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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