The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo

  • Authors:
    • Kai-Sheng Liu
    • Wei-Chao Ding
    • Shao-Xiang Wang
    • Zhong Liu
    • Guo-Wen Xing
    • Ying Wang
    • Yi-Fei Wang
  • View Affiliations

  • Published online on: March 22, 2012     https://doi.org/10.3892/or.2012.1738
  • Pages: 1904-1910
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Abstract

SNX-2112 is a selective heat shock protein 90 (Hsp90) inhibitor which can exert a potent anticancer activity. In this study, we investigated the effects of SNX-2112 on B16 melanoma cells in vitro and in vivo. The 3-(4,5-dimetrylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis demonstrated that SNX-2112 dose-dependently inhibited the growth of B16 cells, and induced G0/G1 cell cycle arrest and apoptosis. Western blotting revealed that SNX-2112 lead to the degradation of Hsp90 client proteins including Akt, IKKα, NF-κB, B-Raf and GSK3β. Furthermore, we assessed the antitumor effect of SNX-2112 in vivo, using a xenograft model in C57BL/6 mice. Oral administration of SNX-2112 significantly inhibited the growth of B16 tumors in mice, with a 47% inhibition observed at dose of 80 mg/kg/day for 15 days, compared to control tumors. Hematoxylin-eosin (H&E) staining of xenograft tissues showed that SNX-2112 also inhibited angiogenesis and lead to a lower blood vessel density in the tumors, compared to the control group. These findings demonstrate that SNX-2112 can exhibit a potent anticancer activity against B16 melanoma cells both in vitro and in vivo, by inhibiting cell proliferation and inducing cell cycle arrest and apoptosis in a mechanism dependent on the degradation of Hsp90 client proteins.

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June 2012
Volume 27 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu K, Ding W, Wang S, Liu Z, Xing G, Wang Y and Wang Y: The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo. Oncol Rep 27: 1904-1910, 2012
APA
Liu, K., Ding, W., Wang, S., Liu, Z., Xing, G., Wang, Y., & Wang, Y. (2012). The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo. Oncology Reports, 27, 1904-1910. https://doi.org/10.3892/or.2012.1738
MLA
Liu, K., Ding, W., Wang, S., Liu, Z., Xing, G., Wang, Y., Wang, Y."The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo". Oncology Reports 27.6 (2012): 1904-1910.
Chicago
Liu, K., Ding, W., Wang, S., Liu, Z., Xing, G., Wang, Y., Wang, Y."The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell growth in vitro and in vivo". Oncology Reports 27, no. 6 (2012): 1904-1910. https://doi.org/10.3892/or.2012.1738