VSP-17, a New PPARγ Agonist, Suppresses the Metastasis of Triple-Negative Breast Cancer via Upregulating the Expression of E-Cadherin

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 1; p. 121
• Main Authors: Wang, Yuhui, Zhu, Menglin, Yuan, Bo, Zhang, Kefeng, Zhong, Mingli, Yi, Wei, Xu, Xiaotian, Duan, Xiaoqun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.01.2018; MDPI
• Subjects: agonist; Breast cancer; Calcium channels; CD36 antigen; CXCL12 protein; E-cadherin; Gelatinase B; Gene expression; Liver; Metastases; Metastasis; Orai1 protein; PPARγ; Reporter gene; STIM1 protein; triple-negative breast cancer; Vascular endothelial growth factor; Viability; VSP-17; Xenografts; triple-negative breast cancer; agonist; metastasis; E-cadherin; PPARγ; VSP-17
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23010121

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, shows higher metastases and relapse rates than other subtypes. The metastasis of TNBC is the main reason for the death of TNBC patients. Increasing evidence has shown that inhibiting the metastasis of TNBC is a good method for TNBC treatment. Here, VSP-17 was designed and synthesized as an agonist of PPARγ, evidenced by upregulating the expression of CD36 and increasing the activity of PPARγ reporter gene. VSP-17 obviously inhibited the migration and invasion process of MDA-MB-231 cells but showed little effect on the viability of MDA-MB-231 cells. Notably, VSP-17 could selectively promote the expression of E-cadherin without affecting the expression of BRMS1, CXCL12, MMP9, Orai1, Stim1, TGF-β, and VEGF. In addition, VSP-17 significantly suppressed the metastasis of liver and promoted the expression of E-cadherin in MDA-MB-231 xenograft model. In conclusion, VSP-17 inhibited the metastasis process of TNBC via upregulating the expression of E-cadherin.