Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer

Tsuyoshi Ueno, Kazunori Tsukuda, Shinichi Toyooka, Midori Ando, Munenori Takaoka, Junichi Soh, Hiroaki Asano, Yuho Maki, Takayuki Muraoka, Norimitsu Tanaka, Kazuhiko Shien, Masashi Furukawa, Tomoki Yamatsuji, Katsuyuki Kiura, Yoshio Naomoto, Shinichiro Miyoshi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The anti-tumor activity of a newly developed Hsp90 inhibitor, NVP-AUY922 (AUY922), against non-small cell lung cancer (NSCLC) was examined. Twenty-one NSCLC cell lines were used, the somatic alterations of which were characterized. Cell proliferation was analyzed using a modified MTS assay. Expression of the client proteins was assessed using Western blotting. The cell cycle was analyzed using flow cytometry. The IC 50 value of AUY922 for the NSCLC cell lines ranged from 5.2 to 860nM (median, 20.4nM). Based on previous data, cells with an IC 50 of less than 50nM were classified as sensitive cells and 19 of the 21 NSCLC cell lines were judged to be sensitive. The IC 50 of five malignant pleural mesothelioma (MPM) cell lines revealed that the MPM cells had a significantly higher IC 50 value (median, 89.2nM; range, 22.2-24,100nM) than the NSCLC cells (p=0.015). There was significant depletion of both the total and phosphorylated client proteins - EGFR, MET, HER2 and AKT - at low drug concentrations (50-100nM) in drug-sensitive cell lines. Cell-cycle analysis was performed for two sensitive cell lines, H1975 and H838. Following AUY922 treatment, an increase in the sub-G 0-G 1 cell population, as well as appearance of cleaved PARP expression, indicated the induction of apoptosis. In conclusion, AUY922 was effective against most NSCLC cell lines, independent of the type of known molecular alteration, and appears to be a promising new drug for the treatment of NSCLC.

Original languageEnglish
Pages (from-to)26-31
Number of pages6
JournalLung Cancer
Volume76
Issue number1
DOIs
Publication statusPublished - Apr 2012

Keywords

  • AUY922
  • EGFR
  • EGFR-TKI
  • Hsp90
  • Mesothelioma
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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  • Cite this

    Ueno, T., Tsukuda, K., Toyooka, S., Ando, M., Takaoka, M., Soh, J., Asano, H., Maki, Y., Muraoka, T., Tanaka, N., Shien, K., Furukawa, M., Yamatsuji, T., Kiura, K., Naomoto, Y., & Miyoshi, S. (2012). Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer. Lung Cancer, 76(1), 26-31. https://doi.org/10.1016/j.lungcan.2011.09.011