Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells

  • Authors:
    • Hwa Jun Cha
    • Jung Hye Choi
    • In Chul Park
    • Chun Ho Kim
    • Sung Kwan An
    • Tae Jin Kim
    • Jae Ho Lee
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  • Published online on: March 15, 2017     https://doi.org/10.3892/ijo.2017.3913
  • Pages: 1279-1288
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Abstract

Epithelial ovarian cancer is the most aggressive and lethal among the gynecological malignancies, which is often found disseminated to peritoneal cavity at the time of diagnosis. There is accumulating evidence on the existence of genetic alteration and amplification of fibroblast growth factor receptor (FGFR) in various cancers. Also the aberrated FGFR/FGF signaling has been implicated in cancer development and tumor microenvironment. However, the antitumor activity of BGJ398, a selective inhibitor of FGFR 1/2/3 against ovarian cancer still remains unknown. The aim of the present study is to evaluate the antitumoral activity of BGJ398 on ovarian cancer cell line SKOV3ip1 using 3-dimensional (3D) sphere culture system which has been accepted as a better mimic in vivo microenvironment than conventional 2-dimensional (2D) monolayer culture system. We examined the differential expression features of key signaling molecules which have a role in cell survival and proliferation between sphere-cultured SKOV3ip1 cells and monolayer-cultured SKOV3ip1 cells. The phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3) known as survival signaling molecules were upregulated in sphere-cultured SKOV3ip1 cells compared to in monolayer-cultured SKOV3ip1 cells. Next, we evaluated the antitumor activity of BGJ398 in monolayer-cultured SKOV3ip1 cells or sphere-cultured SKOV3ip1 cells. Treatment of BGJ398 did not affect the SKOV3ip1 cell viability in monolayer culture system, but, the cell viability of sphere-cultured SKOV3ip1 cells was markedly reduced by BGJ398. The phosphorylation of AKT and STAT3 was downregulated by BGJ398 in sphere-cultured SKOV3ip1 cells, but not in monolayer cultured-SKOV3ip1 cells. Moreover, combination treatment with BGJ398 and paclitaxel in sphere-cultured SKOV3ip1 showed synergistic inhibitory effect on cell viability. Collectively, our report reveals the BGJ398 is a potent antitumor agent against ovarian cancer and FGFR is a promising therapeutic target to anticancer therapy considering ovarian cancer metastatic microenvironment.
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April-2017
Volume 50 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cha HJ, Choi JH, Park IC, Kim CH, An SK, Kim TJ and Lee JH: Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells. Int J Oncol 50: 1279-1288, 2017
APA
Cha, H.J., Choi, J.H., Park, I.C., Kim, C.H., An, S.K., Kim, T.J., & Lee, J.H. (2017). Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells. International Journal of Oncology, 50, 1279-1288. https://doi.org/10.3892/ijo.2017.3913
MLA
Cha, H. J., Choi, J. H., Park, I. C., Kim, C. H., An, S. K., Kim, T. J., Lee, J. H."Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells". International Journal of Oncology 50.4 (2017): 1279-1288.
Chicago
Cha, H. J., Choi, J. H., Park, I. C., Kim, C. H., An, S. K., Kim, T. J., Lee, J. H."Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells". International Journal of Oncology 50, no. 4 (2017): 1279-1288. https://doi.org/10.3892/ijo.2017.3913