YD277：治疗乳腺癌潜在新药（附原文）

诸平

图1 YD277化学结构式

据《治疗诊断学》（Theranostics）杂志网站2017年6月中旬报道，中国科学院昆明动物研究所（ Kunming Institute of Zoology, Chinese Academy of Sciences）中国科学院与云南省动物模型和人类疾病机理重点实验室（Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province）肿瘤生物学学科组陈策实（Ceshi Chen）团队与广州医科大学附属医院惠州第三人民医院实验医学部（Department of Laboratory Medicine, Huizhou No.3 People's Hospital, Affiliated hospital of Guangzhou Medical University）、锦州医科大学上海市奉贤区中心医院研究生培养基地（Fengxian District Center Hospital Graduate Student Training Base, Jinzhou Medical University, Shanghai）、南方医科大学奉贤附属医院实验医学部与中心实验室（Department of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian Hospital）以及美国德克萨斯大学医学部药理学与毒理学系化学生物学课题组（Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch）的研究人员合作研究发现，小分子化合物YD277通过激活内质网应激抑制三阴性乳腺癌，这意味着发现了一种有效治疗三阴性乳腺癌的潜在新药。此项研究成果于2017年6月11日已经在开放存取（Open Access）期刊《治疗诊断学》（Theranostics）网站发表——Zekun Chen, Qiuju Wu, Ye Ding, Wenhui Zhou, Rong Liu, Haiying Chen, Jia Zhou, Jing Feng, Ceshi Chen. YD277 Suppresses Triple-Negative Breast Cancer Partially Through Activating the Endoplasmic Reticulum Stress Pathway（点击可以免费下载原文）. Theranostics 2017; 7(8):2339-2349. doi:10.7150/thno.17555. Available from http://www.thno.org/v07p2339.htm（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，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.