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

  • Published online on: May 24, 2016     https://doi.org/10.3892/ijo.2016.3536
  • Pages: 682-690
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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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August-2016
Volume 49 Issue 2

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

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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