Abstract：
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.
摘要：
三阴性乳腺癌（TNBC）是一种侵袭性亚型，预后不良。硫链菌素对包括TNBC在内的几种癌症具有抗肿瘤活性。本文讨论了硫链菌素在TNBC中的新分子机制。硫链菌素抑制MDA-MB-231细胞活力，伴随着c-FLIP和p-SMAD2/3的减少。c-FLIP过表达降低MDA-MB-231细胞对硫链菌素的敏感性,SMAD2/3敲除增加MDA-MB-231细胞对硫链菌素的敏感性。此外，c-FLIP过表达显著增加SMAD2/3蛋白的表达和磷酸化,反之亦然。总之,我们的研究揭示了c-FLIP/SMAD2/3信号通路是硫链菌素抗肿瘤活性的新机制。
