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Article

ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation

  • Authors:
    • Xiangchao Meng
    • Baoshan Hu
    • Mohammad Monir Hossain
    • Guofu Chen
    • Ying Sun
    • Xuepeng Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Oncology, Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, International Education College, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Pathology, Basic Scientific Medical College, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
  • Pages: 682-690
    |
    Published online on: May 24, 2016
       https://doi.org/10.3892/ijo.2016.3536
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Abstract

A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to observe the effects of ADAM17 small interfering RNA (ADAM17-siRNA) on human MCF-7 breast cancer and investigate its activation pathway. In vitro, MCF-7 cells were divided into ADAM17-siRNA groups, nonsense siRNA groups, AG1478 (selective EGFR blocker) groups, LY294002 [phosphatidylinositol 3-kinase (PI3K) phosphorylation inhibitor] groups, PD0325901 [mitogen extracellular kinase (MEK) inhibitor] groups and control groups. In vivo, MCF-7 cells were implanted subcutaneously into nude mice and then these mice were randomly divided into ADAM17-siRNA groups, vector groups and control groups. Our data showed that compared with the control groups, ADAM17-siRNA, AG1478 and LY294002 could inhibit the migration and proliferation of MCF-7 cells, but PD0325901 and nonsense siRNA did not show this effect. Except that specific ADAM17-siRNA could inhibit the expression of ADAM17 mRNA, others did not change it. Western blot analysis further confirmed that EGFR-PI3K-AKT signaling pathway is involved in ADAM17-siRNA inhibiting migration and proliferation of MCF-7 cells. Similarly to the former, the growth of MCF-7 breast cancer in nude mice was significantly inhibited by ADAM17-siRNA. Compared with the control group and the vector group, the tumor volume was smaller in the ADAM17-siRNA group, the tissues developed large areas of necrosis, immunohistochemistry showed low expressions of ADAM17 and Ki-67 and western blot analysis proved that the expression of ADAM17 protein in the tissue was also reduced. The present study suggests that ADAM17-siRNA inhibits MCF-7 breast cancer and is activated through the EGFR-PI3K-AKT signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Meng X, Hu B, Hossain MM, Chen G, Sun Y and Zhang X: ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. Int J Oncol 49: 682-690, 2016.
APA
Meng, X., Hu, B., Hossain, M.M., Chen, G., Sun, Y., & Zhang, X. (2016). ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. International Journal of Oncology, 49, 682-690. https://doi.org/10.3892/ijo.2016.3536
MLA
Meng, X., Hu, B., Hossain, M. M., Chen, G., Sun, Y., Zhang, X."ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation". International Journal of Oncology 49.2 (2016): 682-690.
Chicago
Meng, X., Hu, B., Hossain, M. M., Chen, G., Sun, Y., Zhang, X."ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation". International Journal of Oncology 49, no. 2 (2016): 682-690. https://doi.org/10.3892/ijo.2016.3536
Copy and paste a formatted citation
x
Spandidos Publications style
Meng X, Hu B, Hossain MM, Chen G, Sun Y and Zhang X: ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. Int J Oncol 49: 682-690, 2016.
APA
Meng, X., Hu, B., Hossain, M.M., Chen, G., Sun, Y., & Zhang, X. (2016). ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. International Journal of Oncology, 49, 682-690. https://doi.org/10.3892/ijo.2016.3536
MLA
Meng, X., Hu, B., Hossain, M. M., Chen, G., Sun, Y., Zhang, X."ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation". International Journal of Oncology 49.2 (2016): 682-690.
Chicago
Meng, X., Hu, B., Hossain, M. M., Chen, G., Sun, Y., Zhang, X."ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation". International Journal of Oncology 49, no. 2 (2016): 682-690. https://doi.org/10.3892/ijo.2016.3536
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