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 Citations (Scopus)

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

Fingerprint

Growth Inhibitors
Neuroblastoma
Heterografts
Local Area Networks
tanespimycin
Nude Mice
HSP90 Heat-Shock Proteins
Neoplasms
Proteins
Molecular Chaperones
Proxy
Signal Transduction
Western Blotting
Apoptosis
Drug Therapy
Therapeutics
Growth
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Geldanamycin
  • Hsp90 inhibitor
  • Neuroblastoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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.

Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors. / Kang, Junghee; Kamal, Adeela; Burrows, Francis J.; Evers, B. Mark; Chung, Dai H.

In: Anticancer Research, Vol. 26, No. 3 A, 01.05.2006, p. 1903-1908.

Research output: Contribution to journalArticle

Kang, J, Kamal, A, Burrows, FJ, Evers, BM & Chung, DH 2006, 'Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors', Anticancer Research, vol. 26, no. 3 A, pp. 1903-1908.
Kang J, Kamal A, Burrows FJ, Evers BM, Chung DH. Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors. Anticancer Research. 2006 May 1;26(3 A):1903-1908.
Kang, Junghee ; Kamal, Adeela ; Burrows, Francis J. ; Evers, B. Mark ; Chung, Dai H. / Inhibition of neuroblastoma xenograft growth by Hsp90 inhibitors. In: Anticancer Research. 2006 ; Vol. 26, No. 3 A. pp. 1903-1908.
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