英國科學(xué)家日前發(fā)現(xiàn)了一種讓健康細胞控制癌細胞,，進而阻止其向腫瘤發(fā)展的新方法，為治療早期癌癥提供了一種全新的手段,。
英國曼徹斯特大學(xué)的研究人員在最近出版的《英國癌癥雜志》（BJC）上報告了這項研究成果,，指出他們發(fā)現(xiàn)了一種被稱為“激酶抑制劑”的特殊化學(xué)藥品種類，開啟了細胞層面上的交流,，即讓健康細胞能夠與癌細胞進行“對話”,。已開發(fā)出來的化學(xué)藥品是一種激酶抑制劑。激酶是一種特殊形式的酶,，它利用磷酸鹽來加速人體內(nèi)的生物過程,。可以阻止這種行為的化學(xué)藥品被稱為激酶抑制劑,。
與妻子Lynne Hampson博士共同開展這項研究的Ian Hampson博士說：“當(dāng)我們把這種化學(xué)藥品加入到混合著健康細胞與癌細胞的燒瓶中時,，患病細胞停止繁殖,，并且再次開始像正常細胞那樣活動。”他補充說：“進一步的測試顯示,，這種化學(xué)藥品可以幫助癌細胞形成與周圍健康細胞的聯(lián)系,，從而讓這些正常的細胞控制癌細胞分裂的機制，并使后者逐漸脫離這種機制的控制,。”
作為人體正常修復(fù)過程的一部分,，細胞分裂是人體器官和組織中自然且不斷發(fā)生的現(xiàn)象，用以補充細胞的損耗,，但是在癌癥病人身上,，細胞分裂是毫無章法的。Hampson說,，新的發(fā)現(xiàn)讓人興奮,，因為與索爾福德大學(xué)的同事開發(fā)的這種化學(xué)藥品看起來是相對無毒的，而其對癌細胞所產(chǎn)生的積極作用甚至在藥品被取走后依然存在,。
“當(dāng)將化學(xué)藥品加入到只有癌細胞的器皿中時,，幾乎沒有什么效用。”Hampson說,，“只有當(dāng)我們把化學(xué)藥品加入到癌細胞與正常細胞混合的器皿中時——類似于它們在體內(nèi)的存在方式,，繁殖才能停止。”他說：“有意思的是,，讓健康細胞與癌細胞之間進行交流的聯(lián)系在激酶抑制劑被取走后依然存在,，顯示出以這種化學(xué)藥品為基礎(chǔ)的藥物可以用于短期治療。”
Hampson說：“此外,，化學(xué)藥品是無毒的,，而且不會像常規(guī)癌癥治療那樣將癌細胞殺死，如化學(xué)療法和放射療法,。所以如果我們可以開發(fā)出一種藥物,，那么它可能極少有副作用。”
Hampson的團隊表示,，他們下一階段的研究將是研究化學(xué)藥品如何能夠增加癌細胞與正常細胞之間的聯(lián)系,。一旦有所發(fā)現(xiàn)，那么就有望生產(chǎn)基于這些化學(xué)藥品且可能在人類身上使用的藥物,。Lynne Hampson補充說：“目前,，我們正在申請資金，在生物化學(xué)方面開展進一步的研究,，研究這些化學(xué)藥品是如何發(fā)揮我們已觀察到的作用的,。我們還打算研究使用不同種類的細胞來評估這些化學(xué)藥品的能力和適用范圍。”
Hampson說，在任何新的藥物治療開始使用之前,，還有更多的工作需要做,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
