来自华中科技大学、第四军医大学和沈阳药科大学等处的研究人员发表了“pantoprazole, a FDA-approved proton-pump inhibitor,suppresses colorectal cancer growth by targeting T-cell-originated proteinkinase”的文章，发现治疗胃溃疡的药物——泮托拉唑能够靶向一种叫做TOpK的蛋白激酶，抑制结直肠癌的生长。

这一发现及相关研究成果发表在国际知名癌症期刊《肿瘤靶点》杂志（Oncotarget）。文章的第一作者为在读研究生曾孝玉、刘林和郑梦竹等同学，朱峰教授、李华教授和段秋红教授等是该文的通讯作者。


“TOpK是英文“T-LAK细胞来源的蛋白激酶”的缩写，在诸如结直肠癌、肺癌、宫颈癌、前列腺癌、乳腺癌、肝癌、胰腺癌等多种人类主要恶性肿瘤中呈强表达，而且其表达量与癌症的恶性程度呈正相关、与疾病的预后呈负相关。它参与了肿瘤细胞增殖、迁移、侵袭和凋亡过程，为肿瘤细胞特异性高表达的蛋白，是癌症靶向治疗的最新重要靶点，TOpK抑制剂有望以很小的副作用而达到治疗肿瘤的效果。

研究人员应用基于蛋白质结构的药物发现方法，从已知药物数据库中筛选出泮托拉唑作为TOpK激酶的抑制剂，并在随后的细胞、整体动物水平证明它能够靶向TOpK激酶、显著抑制小鼠结直肠癌的生长。泮托拉唑是目前临床应用于胃溃疡治疗的常见药物，这里首次发现它可以用于癌症的治疗。其毒副作用小，有希望成为针对此靶点的第一个靶向抗肿瘤药物，小毒甚至无毒地治疗癌症，为提高癌症治疗疗效、降低花费贡献力量。

目前，这一重要研究成果正由武汉华杰世纪生物医药有限公司进行深入挖掘，将泮托拉唑作为改变适应症的改良型新药进行申报，并寻找和开发以泮托拉唑为先导化合物的创新药物，为癌症靶向治疗提供一种新的途径。


原文摘要：
pantoprazole, a FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase

T-cell-originated protein kinase (TOpK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. pantoprazole (ppZ) was identified to be a TOpK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOpK activities by directly binding with TOpK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOpK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOpK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOpK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOpK inhibitor both in vitro and in vivo.