Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors

Junghee Kang, Adeela Kamal, Francis J. Burrows, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Advanced-stage neuroblastomas are often resistant to chemotherapy. Heat shock protein (Hsp) 90 is a molecular chaperons that maintains the stability of important signal transduction proteins. We have previously reported that geldanamycin (GA), an Hsp90 inhibitor, decreases Raf-1 and Akt protein expressions and induces apoptosis in neuroblastoma cells. We sought to determine the in vivo effects of Hsp90 inhibitor compounds on human neuroblastomas. Materials and Methods: Human neuroblastoma (LAN-1 and SK-N-SH) xenografts (4-mm3 tumor implants) were placed in the flanks of athymic nude mice. The mice received either Hsp90 inhibitors (17-AAG or EC5) or vehicle (control). The tumor dimensions were measured twice weekly. Proteins were extracted for Western immunoblotting. Results: Hsp90 inhibitor compounds significantly blocked both LAN-1 and SK-N-SH neuroblastoma growth in vivo. Drug-treated tumors showed decreases in Raf-1 and cleaved PARP expressions. Conclusion: Hsp90 inhibitors may prove to be important novel therapeutic agents for patients with advanced-stage neuroblastoma who fail to respond to current treatment regimens.

Original languageEnglish (US)
Pages (from-to)1903-1908
Number of pages6
JournalAnticancer Research
Volume26
Issue number3 A
StatePublished - May 1 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Geldanamycin
  • Hsp90 inhibitor
  • Neuroblastoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kang, J., Kamal, A., Burrows, F. J., Evers, B. M., & Chung, D. H. (2006). Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors. Anticancer Research, 26(3 A), 1903-1908.