Guangxi Colleges and Universities Key Laboratory of Pharmacology, Guilin Medical University, 109 Huanchengbei Road Two, Guilin 541004, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Molecules. 2018 Jan 8;23(1):121. 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.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，其转移和复发率高于其他亚型。TNBC 的转移是导致 TNBC 患者死亡的主要原因。越来越多的证据表明，抑制 TNBC 的转移是治疗 TNBC 的一种有效方法。在这里，设计并合成了 VSP-17 作为 PPARγ 的激动剂，通过上调 CD36 的表达并增加 PPARγ 报告基因的活性来证明。VSP-17 明显抑制了 MDA-MB-231 细胞的迁移和侵袭过程，但对 MDA-MB-231 细胞的活力几乎没有影响。值得注意的是，VSP-17 可以选择性地促进 E-cadherin 的表达，而不影响 BRMS1、CXCL12、MMP9、Orai1、Stim1、TGF-β和 VEGF 的表达。此外，VSP-17 显著抑制了肝转移，并在 MDA-MB-231 异种移植模型中促进了 E-cadherin 的表达。总之，VSP-17 通过上调 E-cadherin 的表达抑制了 TNBC 的转移过程。
