PAX3-FKHR sensitizes human alveolar rhabdomyosarcoma cells to camptothecin-mediated growth inhibition and apoptosis

Cancer Lett. 2009 Nov 1;284(2):157-64. doi: 10.1016/j.canlet.2009.04.016. Epub 2009 May 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Camptothecin / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / antagonists & inhibitors
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / physiology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, Reporter
  • Humans
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Rhabdomyosarcoma, Alveolar / drug therapy
  • Rhabdomyosarcoma, Alveolar / genetics
  • Rhabdomyosarcoma, Alveolar / metabolism*
  • Rhabdomyosarcoma, Alveolar / pathology
  • Transcription, Genetic


  • Antineoplastic Agents, Phytogenic
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • RNA, Small Interfering
  • Camptothecin