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VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway

  • Authors:
    • Xiaotian Xu
    • Meng Liu
    • Yingying Yang
    • Chengqiong Wei
    • Xiyang Zhang
    • Hengzhi Song
    • Yuhui Wang
    • Xiaoqun Duan

  • View Affiliations

  • Published online on: December 30, 2020     https://doi.org/10.3892/or.2020.7916
  • Pages: 975-986

  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

VSP‑17, a novel peroxisome proliferator‑activated receptor γ (PPARγ) agonist, has been previously demonstrated to suppress the metastasis of triple‑negative breast cancer (TNBC) by upregulating the expression levels of E‑cadherin, which is a key marker of epithelial‑mesenchymal transition (EMT). However, the mechanism of action of VSP‑17, in particular whether it may be associated with the EMT process, remains unknown. The present study investigated the ability of VSP‑17 to inhibit the invasiveness and migratory ability of TNBC cell lines (MDA‑MB‑231 and MDA‑MB‑453) performed in in vitro experiments. including cell migration assay, cell invasion assay, cell transfection, RT‑qPCR, western blot (WB) analysis and immunofluorescence. The present study aimed to ascertain whether and how the PPARγ/AMP‑activated protein kinase (AMPK) signaling pathway serves a role in the inhibitory effects of VSP‑17 on cell migration and invasion. The results revealed that both treatment with compound C (an AMPK inhibitor) and transfection with small interfering RNA (si)AMPK notably diminished the inhibitory effect of VSP‑17 treatment on the migration and invasion of MDA‑MB‑231 and MDA‑MB‑453 cells, indicating that VSP‑17 may, at least partly, exert its effects via AMPK. Furthermore, both compound C and siAMPK markedly diminished the VSP‑17‑induced downregulation of vimentin expression levels and upregulation of E‑cadherin expression levels, further indicating that the VSP‑17‑induced inhibition of the EMT process may be dependent on AMPK. The combination of GW9662 (a PPARγ antagonist) or siPPARγ diminished the inhibitory effect of VSP‑17 treatment on the migration and invasion of the TNBC cells, indicating that PPARγ may serve an important role in the VSP‑17‑induced inhibition of the migration and invasion of TNBC cells. In addition, both GW9662 and siPPARγ significantly reversed the VSP‑17‑induced downregulation of vimentin expression levels and upregulation of E‑cadherin expression levels, implying that the VSP‑17‑induced inhibition of the EMT process may be dependent on PPARγ. VSP‑17 treatment also upregulated the expression levels of p‑AMPK, which could be reversed by either GW9662 or siPPARγ, indicating that the VSP‑17‑induced activation of the AMPK signaling pathway was PPARγ‑dependent. In conclusion, the findings of the present study indicated that VSP‑17 treatment may inhibit the migration and invasion of TNBC cells by suppressing the EMT process via the PPARγ/AMPK signaling pathway.
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March-2021
Volume 45 Issue 3

Print ISSN: 1021-335X
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Spandidos Publications style
Xu X, Liu M, Yang Y, Wei C, Zhang X, Song H, Wang Y and Duan X: VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway. Oncol Rep 45: 975-986, 2021
APA
Xu, X., Liu, M., Yang, Y., Wei, C., Zhang, X., Song, H. ... Duan, X. (2021). VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway. Oncology Reports, 45, 975-986. https://doi.org/10.3892/or.2020.7916
MLA
Xu, X., Liu, M., Yang, Y., Wei, C., Zhang, X., Song, H., Wang, Y., Duan, X."VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway". Oncology Reports 45.3 (2021): 975-986.
Chicago
Xu, X., Liu, M., Yang, Y., Wei, C., Zhang, X., Song, H., Wang, Y., Duan, X."VSP‑17 suppresses the migration and invasion of triple‑negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway". Oncology Reports 45, no. 3 (2021): 975-986. https://doi.org/10.3892/or.2020.7916