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Article

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
  • View Affiliations / Copyright

    Affiliations: Osan University, Department of Skin Care and Beauty, Osan, Gyeonggi-do 18119, Republic of Korea, Department of Oriental Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea, Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea, Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Science, Seoul 139240, Republic of Korea, Molecular-Targeted Drug Research Center, Konkuk University, Seoul 05029, Republic of Korea, Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea, Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul 04619, Republic of Korea
  • Pages: 1279-1288
    |
    Published online on: March 15, 2017
       https://doi.org/10.3892/ijo.2017.3913
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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