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科学网YD277:治疗乳腺癌潜在新药(附原文)

作者:admin 发布时间:2017.11.22 浏览:

. Theranostics 2017; 7(8):2339-2349. doi:10.7150/thno.17555. Available from (点击可以免费下载原文).

  乳腺癌是一种常见的女性恶性肿瘤,严重危害着女性身心健康。其中,三阴性乳腺癌(TNBC)由于缺乏有效的治疗靶点, 出国看病 ,患者在传统的手术、化疗、放疗后治疗效果不佳,易出现复发和转移,因此目前急需寻找新的治疗靶点和有效药物来提高患者生存率。更多信息可以浏览原文。

Abstract

Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor clinical outcomes. YD277 is a novel small molecule derived from ML264, a KLF5 inhibitor that elicits cytotoxic effects in colon cancer cell lines. Our previous studies suggest that Krüpple-like factor 5 (KLF5) is a promising therapeutic target for TNBC. In this study, we demonstrated that YD277 significantly induced G1 cell cycle arrest and apoptosis in MDA-MB-231 and MDA-MB-468 TNBC cells, independent of KLF5 inhibition. YD277 also reduced the protein expression levels of Cyclin D1, Bcl2 and Bclxl and promoted the expression of p21 and p27. Moreover, the pro-apoptotic activity of YD277 in TNBC was mediated by the transcription of IRE1α, a key molecule in the endoplasmic reticulum (ER) stress pathway. Finally, YD277 (15 mg/kg) significantly suppressed the growth of MDA-MB-231 tumor xenografts in nude mice. These findings indicate that YD277 is a promising chemotherapeutic candidate for TNBC.

Keywords: YD277, KLF5, Triple-Negative Breast Cancer, IRE1α, ER stress.





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