我公司郭玉明和劉詩洋博士在國際腫瘤權(quán)威雜志“Oncotarget”發(fā)表SNG1153治療肺癌研究的最新進(jìn)展
2016年6月6日，中國北京
北京珅奧基醫(yī)藥科技有限公司劉詩洋和郭玉明博士（共同第一作者）及其課題組于2016年6月2日在國際知名癌癥期刊《Oncotarget》（腫瘤靶點(diǎn), 影響因子6.4）在線發(fā)表了一篇名為“ A novel anticancer agent SNG1153 inhibits growth of lung cancer stem/progenitor cells” (即“一種全新抗癌藥物SNG1153抑制肺癌干細(xì)胞的生長”原文鏈接：http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=9783&author-preview=7jr）的文章。
肺癌在全球范圍內(nèi)是致死率最高的惡性腫瘤之一。已有研究證實(shí)肺癌中活躍著具有干細(xì)胞性質(zhì)的細(xì)胞稱之為肺癌干細(xì)胞。這部分肺癌干細(xì)胞對現(xiàn)有的多種治療手段會(huì)產(chǎn)生強(qiáng)烈的耐藥性。因此，找到抑制這群干細(xì)胞的藥物是肺癌治療的當(dāng)務(wù)之急。在此項(xiàng)研究中我們首次發(fā)現(xiàn)一種新的化學(xué)藥物SNG1153 能夠抑制肺癌干細(xì)胞。SNG1153是北京珅奧基醫(yī)藥科技有限公司基于阿可拉定設(shè)計(jì)的全新的且具有自主知識產(chǎn)權(quán)的新一代化合物藥物。該研究表明SNG1153能夠抑制肺癌細(xì)胞的增殖，并引起肺癌細(xì)胞凋亡。更為重要的是該研究發(fā)現(xiàn)SNG1153有效抑制肺癌干細(xì)胞球形成，減少CD133（肺癌干細(xì)胞標(biāo)志物）表達(dá)。體內(nèi)模型研究發(fā)現(xiàn)SNG1153能夠降低肺癌干細(xì)胞在免疫缺陷性小鼠上的成瘤能力。通過進(jìn)一步機(jī)制研究發(fā)現(xiàn)SNG1153抗肺癌干細(xì)胞的作用依賴于β-catenin信號通路。SNG1153能夠磷酸化β-catenin進(jìn)而促進(jìn)β-catenin降解，最終抑制肺癌干細(xì)胞的生長。該研究在國際上首次證明SNG1153具有抑制肺癌干細(xì)胞的作用，同時(shí)提示將SNG1153研發(fā)成治療肺癌的全新藥物的廣闊前景。
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.