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Article Open Access

Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling

  • Authors:
    • Juan Xiao
    • Manman Xu
    • Teng Hou
    • Yongwen Huang
    • Chenlu Yang
    • Jundong Li
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
    Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 3249-3256
    |
    Published online on: May 14, 2015
       https://doi.org/10.3892/mmr.2015.3784
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Abstract

Src family tyrosine kinase (SFK) activation is associated with ovarian cancer progression. Therefore, SFKs are targets for the development of potential treatments of ovarian cancer. Dasatinib is a tyrosine kinase inhibitor that targets SFK activity, and is used for the treatment of B cell and Abelson lymphomas. At the present time, the potential effect of dasatinib on ovarian cancer is not clear. The aim of the present study was to investigate the antitumor activity of dasatinib, alone and in combination with paclitaxel, in ovarian cancer in vitro and in vivo. In the present study, the expression of Src and phospho‑Src-Y416 (p‑Src) was measured in six ovarian cancer cell lines using western blotting and immunohistochemistry. In addition, cell viability and apoptosis were measured using an MTT assay and annexin V‑fluorescein isothiocyanate staining. An ovarian cancer murine xenograft model was established, in order to evaluate the antitumor effect of dasatinib alone and in combination with paclitaxel in ovarian cancer. High levels of p‑Src protein expression were observed in all cell lines, as compared with healthy cells, which indicated activation of the Src signaling pathway. p‑Src expression increased in ovarian cancer cells following paclitaxel treatment. Dasatinib treatment demonstrated anti‑ovarian cancer properties, by downregulating p‑Src expression and by inducing cancer cell apoptosis. Combined treatment with dasatinib and paclitaxel markedly inhibited proliferation and promoted apoptosis of ovarian cancer cells, compared with control cells. Combined dasatinib and paclitaxel treatment exhibited antitumor activities in vivo and in vitro (combination indices, 0.25‑0.93 and 0.31‑0.75; and tumor growth inhibitory rates, 76.7% and 58.5%, in A2780 and HO8910 cell lines, respectively), compared with paclitaxel treatment alone. Dasatinib monotherapy demonstrated anti‑ovarian cancer activities. The effects of dasatinib and paclitaxel treatments on ovarian cancer cells appeared to be mediated by the Src pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Xiao J, Xu M, Hou T, Huang Y, Yang C and Li J: Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling. Mol Med Rep 12: 3249-3256, 2015.
APA
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., & Li, J. (2015). Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling. Molecular Medicine Reports, 12, 3249-3256. https://doi.org/10.3892/mmr.2015.3784
MLA
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., Li, J."Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling". Molecular Medicine Reports 12.3 (2015): 3249-3256.
Chicago
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., Li, J."Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling". Molecular Medicine Reports 12, no. 3 (2015): 3249-3256. https://doi.org/10.3892/mmr.2015.3784
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao J, Xu M, Hou T, Huang Y, Yang C and Li J: Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling. Mol Med Rep 12: 3249-3256, 2015.
APA
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., & Li, J. (2015). Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling. Molecular Medicine Reports, 12, 3249-3256. https://doi.org/10.3892/mmr.2015.3784
MLA
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., Li, J."Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling". Molecular Medicine Reports 12.3 (2015): 3249-3256.
Chicago
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., Li, J."Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling". Molecular Medicine Reports 12, no. 3 (2015): 3249-3256. https://doi.org/10.3892/mmr.2015.3784
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