Open Access

Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells

  • Authors:
    • Eri Takiguchi
    • Masato Nishimura
    • Ayuka Mineda
    • Takako Kawakita
    • Akiko Abe
    • Minoru Irahara
  • View Affiliations

  • Published online on: August 28, 2017     https://doi.org/10.3892/etm.2017.5061
  • Pages: 4293-4299
  • Copyright: © Takiguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto‑oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling in vitro. Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO‑2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST‑1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase‑3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase‑3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Takiguchi E, Nishimura M, Mineda A, Kawakita T, Abe A and Irahara M: Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells. Exp Ther Med 14: 4293-4299, 2017
APA
Takiguchi, E., Nishimura, M., Mineda, A., Kawakita, T., Abe, A., & Irahara, M. (2017). Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells. Experimental and Therapeutic Medicine, 14, 4293-4299. https://doi.org/10.3892/etm.2017.5061
MLA
Takiguchi, E., Nishimura, M., Mineda, A., Kawakita, T., Abe, A., Irahara, M."Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells". Experimental and Therapeutic Medicine 14.5 (2017): 4293-4299.
Chicago
Takiguchi, E., Nishimura, M., Mineda, A., Kawakita, T., Abe, A., Irahara, M."Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4293-4299. https://doi.org/10.3892/etm.2017.5061