北京珅奥基医药科技有限公司刘诗洋和郭玉明博士(共同第一作者)及其课题组于2016年6月2日在国际知名癌症期刊《Oncotarget》(肿瘤靶点, 影响因子6.4)在线发表了一篇名为“ A novel anticancer agent SNG1153 inhibits growth of lung cancer stem/progenitor cells” (即“一种全新抗癌药物SNG1153抑制肺癌干细胞的生长”原文链接:http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=9783&author-preview=7jr)的文章。
肺癌在全球范围内是致死率最高的恶性肿瘤之一。已有研究证实肺癌中活跃着具有干细胞性质的细胞称之为肺癌干细胞。这部分肺癌干细胞对现有的多种治疗手段会产生强烈的耐药性。因此,找到抑制这群干细胞的药物是肺癌治疗的当务之急。在此项研究中我们首次发现一种新的化学药物SNG1153 能够抑制肺癌干细胞。SNG1153是北京珅奥基医药科技有限公司基于阿可拉定设计的全新的且具有自主知识产权的新一代化合物药物。该研究表明SNG1153能够抑制肺癌细胞的增殖,并引起肺癌细胞凋亡。更为重要的是该研究发现SNG1153有效抑制肺癌干细胞球形成,减少CD133(肺癌干细胞标志物)表达。体内模型研究发现SNG1153能够降低肺癌干细胞在免疫缺陷性小鼠上的成瘤能力。通过进一步机制研究发现SNG1153抗肺癌干细胞的作用依赖于β-catenin信号通路。SNG1153能够磷酸化β-catenin进而促进β-catenin降解,最终抑制肺癌干细胞的生长。该研究在国际上首次证明SNG1153具有抑制肺癌干细胞的作用,同时提示将SNG1153研发成治疗肺癌的全新药物的广阔前景。
英文摘要:
Lung cancer is the leading cause of cancer-related death in both men and women. Lung cancer contains a small population of cancer cells with stem-like features known as cancer stem cells (CSCs). CSCs are often more resistant to current therapeutic treatments. Thus, it is urgent to develop a novel agent that is able to inhibit CSCs growth. In this study, we examined the ability of SNG1153, a novel chemical agent to inhibit the growth of lung CSCs. We found that SNG1153 inhibited growth and induced apoptosis in established lung cancer cells. We also found that SNG1153 inhibited the tumorsphere formation and decreased CD133-positive (lung CSC marker) cancer cells. SNG1153 was able to attenuate tumor formation in NOD/SCID (non-obese diabetic/ severe combined immunodeficient) mice injected with lung tumorsphere cells. We further demonstrated that SNG1153 induced β-catenin phosphorylation and down-regulated β-catenin. Our results thus demonstrate that SNG1153 effectively inhibits the growth of lung CSCs and suggest that SNG1153 may be a novel therapeutic agent to treat human lung cancer.
来源:盛诺基官网