Open Access

Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways

  • Authors:
    • Ai‑Lei Wang
    • Yong Li
    • Qun Zhao
    • Li‑Qiao Fan
  • View Affiliations

  • Published online on: April 5, 2018     https://doi.org/10.3892/mmr.2018.8857
  • Pages: 7721-7729
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Formononetin (Form), a phytoestrogen extracted from the roots of Astragalus membranaceus, is one of the fundamental herbs used in traditional Chinese medicine because of its protective effects against certain malignant tumors. However, its role in colon carcinoma cells and the underlying molecular mechanisms have not been completely elucidated. The present study aimed to demonstrate that Form significantly inhibited the proliferation and invasion of the colon carcinoma cell lines SW1116 and HCT116. Mechanistic studies have suggested that Form suppresses colon carcinoma cell growth by downregulating cell cycle‑associated protein (cyclin D1) expression and arresting the cell cycle at the G0‑G1 checkpoint. Further studies revealed that treatment with Form inhibits matrix metalloproteinase (MMP)2 and MMP9 expression. Aditionally, the results demonstrated that Form significantly increased microRNA (miR)‑149 expression. Following miR‑149 overexpression in SW1116 and HCT116 cells using an miR‑149 mimic, cell viability and Ephrin type‑B receptor 3 (EphB3) levels decreased. Furthermore, the inhibitory effects of Form were associated with phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (AKT) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. These results indicated the suppressive effect of Form on colon carcinoma cell proliferation and invasion, possibly via miR‑149‑induced EphB3 downregulation and the inhibition of the PI3K/AKT and STAT3 signaling pathways. Overall, Form may be used as a novel candidate for the clinical treatment of colorectal cancer in the future.
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June-2018
Volume 17 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang AL, Li Y, Zhao Q and Fan LQ: Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Mol Med Rep 17: 7721-7729, 2018
APA
Wang, A., Li, Y., Zhao, Q., & Fan, L. (2018). Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways. Molecular Medicine Reports, 17, 7721-7729. https://doi.org/10.3892/mmr.2018.8857
MLA
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17.6 (2018): 7721-7729.
Chicago
Wang, A., Li, Y., Zhao, Q., Fan, L."Formononetin inhibits colon carcinoma cell growth and invasion by microRNA‑149‑mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways". Molecular Medicine Reports 17, no. 6 (2018): 7721-7729. https://doi.org/10.3892/mmr.2018.8857