英国科学家日前发现了一种让健康细胞控制癌细胞，进而阻止其向肿瘤发展的新方法，为治疗早期癌症提供了一种全新的手段。
英国曼彻斯特大学的研究人员在最近出版的《英国癌症杂志》（BJC）上报告了这项研究成果，指出他们发现了一种被称为“激酶抑制剂”的特殊化学药品种类，开启了细胞层面上的交流，即让健康细胞能够与癌细胞进行“对话”。已开发出来的化学药品是一种激酶抑制剂。激酶是一种特殊形式的酶，它利用磷酸盐来加速人体内的生物过程。可以阻止这种行为的化学药品被称为激酶抑制剂。
与妻子Lynne Hampson博士共同开展这项研究的Ian Hampson博士说：“当我们把这种化学药品加入到混合着健康细胞与癌细胞的烧瓶中时，患病细胞停止繁殖，并且再次开始像正常细胞那样活动。”他补充说：“进一步的测试显示，这种化学药品可以帮助癌细胞形成与周围健康细胞的联系，从而让这些正常的细胞控制癌细胞分裂的机制，并使后者逐渐脱离这种机制的控制。”
作为人体正常修复过程的一部分，细胞分裂是人体器官和组织中自然且不断发生的现象，用以补充细胞的损耗，但是在癌症病人身上，细胞分裂是毫无章法的。Hampson说，新的发现让人兴奋，因为与索尔福德大学的同事开发的这种化学药品看起来是相对无毒的，而其对癌细胞所产生的积极作用甚至在药品被取走后依然存在。
“当将化学药品加入到只有癌细胞的器皿中时，几乎没有什么效用。”Hampson说，“只有当我们把化学药品加入到癌细胞与正常细胞混合的器皿中时——类似于它们在体内的存在方式，繁殖才能停止。”他说：“有意思的是，让健康细胞与癌细胞之间进行交流的联系在激酶抑制剂被取走后依然存在，显示出以这种化学药品为基础的药物可以用于短期治疗。”
Hampson说：“此外，化学药品是无毒的，而且不会像常规癌症治疗那样将癌细胞杀死，如化学疗法和放射疗法。所以如果我们可以开发出一种药物，那么它可能极少有副作用。”
Hampson的团队表示，他们下一阶段的研究将是研究化学药品如何能够增加癌细胞与正常细胞之间的联系。一旦有所发现，那么就有望生产基于这些化学药品且可能在人类身上使用的药物。Lynne Hampson补充说：“目前，我们正在申请资金，在生物化学方面开展进一步的研究，研究这些化学药品是如何发挥我们已观察到的作用的。我们还打算研究使用不同种类的细胞来评估这些化学药品的能力和适用范围。”
Hampson说，在任何新的药物治疗开始使用之前，还有更多的工作需要做。（生物谷Bioon.com）
生物谷推荐原始出处：
British Journal of Cancer (2009) 101, 829–839. doi:10.1038/sj.bjc.6605208
Analogues of Y27632 increase gap junction communication and suppress the formation of transformed NIH3T3 colonies
L Hampson1, X T He1, A W Oliver1, J A Hadfield2, T Kemp2, J Butler2, A McGown2, H C Kitchener1 and I N Hampson1
1University of Manchester School of Cancer Studies and Imaging Science, Gynaecological Oncology Laboratories, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, UK
2Centre for Molecular Drug Design, Kidscan Laboratories, Cockcroft Building, University of Salford, Manchester M5 4WT, UK
background: Constitutive activation of RhoA-dependent RhoA kinase (ROCK) signalling is known to promote cellular transformation and the ROCK inhibitor Y-27632 has the ability to suppress focus formation of RhoA transformed NIH3T3 cells.
methods: Sixty-four novel structural analogues of Y27632 were synthesised and tested for their ability to persistently inhibit the transformation of NIH3T3 cells by Rho guanidine exchange factor 16 (ARHGEF16) or Ras. In vitro kinase inhibitor profiling, co-culture of transformed cells with non-transformed cells and a novel Lucifer yellow/PKH67 dye transfer method were used to investigate their mode of action.
results: Four Y27632 analogues inhibited transformed focus formation that persisted when the compound was withdrawn. No toxicity was observed against either transformed or non-transformed cells and the effect was dependent on co-culture of these two cell types. In vitro kinase inhibitor profiling indicated that these compounds had reduced activity against ROCK compared with Y27632, targeting instead Aurora A (AURKA), p38 (MAPK14) and Hgk (MAP4K4). Dye transfer analysis showed they increased gap junction intercellular communication (GJIC) between transformed and non-transformed cells.
conclusions: These data are the first to suggest that transient blockade of specific kinases can induce a persistent inhibition of non-contact inhibited transformed colony formation and can also remove pre-formed colonies. These effects could potentially be mediated by the observed increase in GJIC between transformed and non-transformed cells. Selection of kinase inhibitors with this property may thus provide a novel strategy for cancer chemoprevention.
