Hsp90 inhibitor SY‑016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells

  • Authors:
    • Hyun Gyo Lee
    • Won Jin Park
    • So Jin Shin
    • Sang Hoon Kwon
    • Soon Do Cha
    • Young Ho Seo
    • Ju Hui Jeong
    • Ji Yoon Lee
    • Chi Heum Cho
  • View Affiliations

  • Published online on: March 1, 2017     https://doi.org/10.3892/ol.2017.5794
  • Pages: 2817-2822
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Abstract

The aim of the present study was to evaluate the in vitro effect of a heat shock protein (Hsp)90 inhibitor, SY‑016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR‑3PTX, and explore its mechanism of apoptosis. In the present study, SY‑016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug‑resistant tumor cells were established in vitro by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase‑3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY‑016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B‑cell lymphoma (Bcl)-2, X‑linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor‑κB and cyclin-dependent kinase 4, as well as upregulation of Bcl‑2‑associated X protein, were observed. SY‑016 may contribute to the induction of apoptosis in OVCAR‑3PTX cells. These results suggest that SY‑016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX.

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April-2017
Volume 13 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Lee HG, Park WJ, Shin SJ, Kwon SH, Cha SD, Seo YH, Jeong JH, Lee JY and Cho CH: Hsp90 inhibitor SY‑016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells. Oncol Lett 13: 2817-2822, 2017.
APA
Lee, H.G., Park, W.J., Shin, S.J., Kwon, S.H., Cha, S.D., Seo, Y.H. ... Cho, C.H. (2017). Hsp90 inhibitor SY‑016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells. Oncology Letters, 13, 2817-2822. https://doi.org/10.3892/ol.2017.5794
MLA
Lee, H. G., Park, W. J., Shin, S. J., Kwon, S. H., Cha, S. D., Seo, Y. H., Jeong, J. H., Lee, J. Y., Cho, C. H."Hsp90 inhibitor SY‑016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells". Oncology Letters 13.4 (2017): 2817-2822.
Chicago
Lee, H. G., Park, W. J., Shin, S. J., Kwon, S. H., Cha, S. D., Seo, Y. H., Jeong, J. H., Lee, J. Y., Cho, C. H."Hsp90 inhibitor SY‑016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells". Oncology Letters 13, no. 4 (2017): 2817-2822. https://doi.org/10.3892/ol.2017.5794