新浪登录
腾讯登录Oncotarget：新型药物可有效杀灭致癌干细胞
| 导读 | 近日，发表在国际杂志Oncotarget上的一篇研究论文中，来自格拉纳达大学的科学家通过研究开发了一种新型的抵御致癌干细胞的新药，致癌干细胞是引发癌症的关键，由于其存在常常会引发患者化疗后癌症复发及转移，这种新药名为Bozepinib，其在小鼠试验中证实有效。 |
近日，发表在国际杂志Oncotarget上的一篇研究论文中，来自格拉纳达大学的科学家通过研究开发了一种新型的抵御致癌干细胞的新药，致癌干细胞是引发癌症的关键，由于其存在常常会引发患者化疗后癌症复发及转移，这种新药名为Bozepinib，其在小鼠试验中证实有效。
致癌干细胞在肿瘤组织中的含量非常少，其会在包括原发肿瘤位置等其它部位引发癌症的转移，正常情况下致癌干细胞处于休眠状态；常规的化疗及放疗方法仅对已经分化的癌细胞有作用，并不能破坏休眠状态的致癌干细胞，实际上在经历积极的治疗反应后许多癌症患者的病情会因致癌干细胞未被破坏而复发。
过去很多年里，研究人员开展抵御癌症的研究重点集中于一些可以有效选择性攻击致癌干细胞的新药，如果可以有效消除致癌干细胞那么就可以有效治疗癌症，延长患者的生存期。文章中研究者Juan Antonio Marchal教授表示，这种名为Bozepinib的新型药物可以选择性地抵御乳腺癌、结肠癌及皮肤癌中的致癌干细胞，药物Bozepinib的强大抗肿瘤活性取决于其对HER2信号通路的抑制作用，该药物同时也可以一直肿瘤新生血管的形成及扩散。
最后研究者表示，这种新药经腹膜注射或口服对健康小鼠无毒性作用，而且其可以抑制小鼠机体中肿瘤的生长及肺癌的转移；当前研究人员正在进行安全性测试，研究者希望这种新型药物及其衍生物可以在未来有效治疗癌症及癌症复发的患者。（转化医学网360zhyx.com）
本文系转化医学网原创翻译整理，欢迎转载！转载请注明来源并附原文链接。谢谢！
转化医学网推荐的原文摘要：
HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib
Oncotarget doi
Alberto Ramírez1, Houria Boulaiz2,3,4, Cynthia Morata-Tarifa3,4, Macarena Perán1, Gema Jiménez2,3,4, Manuel Picon-Ruiz3,5, Ahmad Agil6, Olga Cruz-López4,7, Ana Conejo-García4,7, Joaquín M. Campos4,7, Ana Sánchez8, María A. García3,4,9, Juan A. Marchal2,3,4
Identification of novel anticancer drugs presenting more than one molecular target and efficacy against cancer stem-like cells (CSCs) subpopulations represents a therapeutic need to combat the resistance and the high risk of relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine], a small anti-tumor compound, demonstrated selectivity on cancer cells and showed an inhibitory effect over kinases involved in carcinogenesis, proliferation and angiogenesis. The cytotoxic effects of Bozepinib were observed in both breast and colon cancer cells expressing different receptor patterns. Bozepinib inhibited HER-2 signaling pathway and JNK and ERKs kinases. In addition, Bozepinib has an inhibitory effect on AKT and VEGF together with anti-angiogenic and anti-migratory activities. Moreover, the modulation of pathways involved in tumorigenesis by Bozepinib was also evident in microarrays analysis. Interestingly, Bozepinib inhibited both mamo- and colono-spheres formation and eliminated ALDH+ CSCs subpopulations at a low micromolar range similar to Salinomycin. Bozepinib induced the down-regulation of c-MYC, β-CATENIN and SOX2 proteins and the up-regulation of the GLI-3 hedgehog-signaling repressor. Finally, Bozepinib shows in vivo anti-tumor and anti-metastatic efficacy in xenotransplanted nude mice without presenting sub-acute toxicity. These findings support further studies on the therapeutic potential of Bozepinib in cancer patients.
Oncotarget doi
Alberto Ramírez1, Houria Boulaiz2,3,4, Cynthia Morata-Tarifa3,4, Macarena Perán1, Gema Jiménez2,3,4, Manuel Picon-Ruiz3,5, Ahmad Agil6, Olga Cruz-López4,7, Ana Conejo-García4,7, Joaquín M. Campos4,7, Ana Sánchez8, María A. García3,4,9, Juan A. Marchal2,3,4
Identification of novel anticancer drugs presenting more than one molecular target and efficacy against cancer stem-like cells (CSCs) subpopulations represents a therapeutic need to combat the resistance and the high risk of relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine], a small anti-tumor compound, demonstrated selectivity on cancer cells and showed an inhibitory effect over kinases involved in carcinogenesis, proliferation and angiogenesis. The cytotoxic effects of Bozepinib were observed in both breast and colon cancer cells expressing different receptor patterns. Bozepinib inhibited HER-2 signaling pathway and JNK and ERKs kinases. In addition, Bozepinib has an inhibitory effect on AKT and VEGF together with anti-angiogenic and anti-migratory activities. Moreover, the modulation of pathways involved in tumorigenesis by Bozepinib was also evident in microarrays analysis. Interestingly, Bozepinib inhibited both mamo- and colono-spheres formation and eliminated ALDH+ CSCs subpopulations at a low micromolar range similar to Salinomycin. Bozepinib induced the down-regulation of c-MYC, β-CATENIN and SOX2 proteins and the up-regulation of the GLI-3 hedgehog-signaling repressor. Finally, Bozepinib shows in vivo anti-tumor and anti-metastatic efficacy in xenotransplanted nude mice without presenting sub-acute toxicity. These findings support further studies on the therapeutic potential of Bozepinib in cancer patients.
还没有人评论，赶快抢个沙发