Open Access

Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer

Retraction in: /10.3892/ijmm.2023.5227

  • Authors:
    • Cong Fan
    • Yunshan Wang
    • Ziming Liu
    • Ying Sun
    • Xiuwen Wang
    • Guangwei Wei
    • Junmin Wei
  • View Affiliations

  • Published online on: May 21, 2015     https://doi.org/10.3892/ijmm.2015.2217
  • Pages: 204-214
  • Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Metformin, a widely prescribed antidiabetic drug, has previously been shown to lower the risk of certain types of cancer, including that of breast cancer, and to improve prognosis. Its anticancer effects, which are mediated by the activation of AMP-activated protein kinase (AMPK), have become notable. The Sonic hedgehog (Shh) signaling pathway is involved in changes in mammary ducts and malignant transformation. The aim of the present study was to elucidate the role of the Shh pathway in mediating the anticancer effects of metformin and the correlation between AMPK and the Shh pathway. We investigated the effectiveness of metformin in inhibiting the proliferation, migration, invasion and stemness of breast cancer cells in vitro using RNA extraction and reverse transcription‑polymerase chain reaction (RT-PCR), western blot analysis, cell proliferation assay, scratch-wound assay (cell migration assay), cell invasion assay, mammosphere culture and flow cytometry. In in vivo experiments, a tumor xenograft model was used to detect the effects of metformin on cancer cell proliferation. The results revealed that the treatment of breast cancer cells with metformin led to the inhibition of the Shh signaling pathway. Importantly, metformin inhibited recombinant human Shh (rhShh)‑induced cell migration, invasion, and stemness, and impaired cell proliferation both in vitro and in vivo. Furthermore, the small interfering RNA (siRNA)‑mediated downregulation of AMPK reversed the inhibitory effects of metformin on rhShh‑induced Gli-1 expression and stemness. Our findings identified a role of the Shh signaling pathway in the anticancer effects of metformin in breast cancer. Furthermore, we revealed that the metformin-mediated inhibition of the Shh signaling pathway may be dependent on AMPK.
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July-2015
Volume 36 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fan C, Wang Y, Liu Z, Sun Y, Wang X, Wei G and Wei J: Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer Retraction in /10.3892/ijmm.2023.5227. Int J Mol Med 36: 204-214, 2015
APA
Fan, C., Wang, Y., Liu, Z., Sun, Y., Wang, X., Wei, G., & Wei, J. (2015). Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer Retraction in /10.3892/ijmm.2023.5227. International Journal of Molecular Medicine, 36, 204-214. https://doi.org/10.3892/ijmm.2015.2217
MLA
Fan, C., Wang, Y., Liu, Z., Sun, Y., Wang, X., Wei, G., Wei, J."Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer Retraction in /10.3892/ijmm.2023.5227". International Journal of Molecular Medicine 36.1 (2015): 204-214.
Chicago
Fan, C., Wang, Y., Liu, Z., Sun, Y., Wang, X., Wei, G., Wei, J."Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer Retraction in /10.3892/ijmm.2023.5227". International Journal of Molecular Medicine 36, no. 1 (2015): 204-214. https://doi.org/10.3892/ijmm.2015.2217