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

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.