杜克大學(xué)醫(yī)學(xué)中心的研究人員指出，在致命的腦癌中,，干細(xì)胞對(duì)放療更具抑制效果,。而在實(shí)驗(yàn)室中，通過(guò)對(duì)這些癌癥干細(xì)胞使用一種藥物阻斷一個(gè)特殊的信號(hào)通路,，并結(jié)合放射治療，研究人員發(fā)現(xiàn)這能夠殺死更多的神經(jīng)膠質(zhì)瘤細(xì)胞,。
這項(xiàng)研究是在早期研究的基礎(chǔ)上進(jìn)行的,。之前的研究表明癌癥干細(xì)胞抑制放療的效果比其他癌細(xì)胞更強(qiáng)。
杜克大學(xué)的研究人員識(shí)別了一種信號(hào)通路,，該通路叫Notch,，其是抑制效果增強(qiáng)的潛在原因。Notch同樣在正常的干細(xì)胞中存在,，對(duì)細(xì)胞之間的交流很重要,。這項(xiàng)研究結(jié)果發(fā)布在11月份后期的的Stem Cells上,。
這是研究人員第一次在放療失敗的腫瘤組織中發(fā)現(xiàn)Notch通道。這項(xiàng)研究的負(fù)責(zé)人Jialiang Wang博士介紹說(shuō),，Notch通路可以作為一個(gè)有前途的藥物靶標(biāo),，開(kāi)發(fā)出正確的藥物或能阻止真正的有害“家伙”-神經(jīng)膠質(zhì)瘤干細(xì)胞。
癌癥中的干細(xì)胞是癌細(xì)胞增殖的來(lái)源,。數(shù)百個(gè)的癌癥干細(xì)胞能夠快速變成百萬(wàn)的腫瘤細(xì)胞,。
研究人員使用了一種叫γ-分泌酶抑制劑的藥物，該藥物能靶向定位Notch通路中一種關(guān)鍵的酶,。
這些抑制劑能夠?qū)鼓[瘤中異常激活的Notch通路,，比如白血病，乳腺癌和腦瘤,。在這項(xiàng)研究中,，該抑制劑單獨(dú)使用只是適度的降低了腫瘤細(xì)胞的生長(zhǎng)，但是在結(jié)合了臨床的放射療法后,，會(huì)引起腫瘤組織中大量的細(xì)胞死亡,，并顯著降低了神經(jīng)膠質(zhì)瘤干細(xì)胞的生存。因此聯(lián)合療法大大增強(qiáng)了對(duì)腫瘤細(xì)胞生長(zhǎng)的抑制,。（生物谷Bioon.com）
生物谷推薦原始出處：
STEM CELLS 17 Nov 2009
Notch Promotes Radioresistance of Glioma Stem Cells
Jialiang Wang 1 2 *, Timothy P. Wakeman 3, Justin D. Lathia 4, Anita B. Hjelmeland 4, Xiao-Fan Wang 3, Rebekah R. White 1 2, Jeremy N. Rich 4 *§, Bruce A. Sullenger 1 2 *
1Department of Surgery, Duke University Medical Center, Durham, NC 27710
2Duke Translational Research Institute, Duke University Medical Center, Durham, NC 27710
3Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
4Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195
Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhanced radiation-induced cell death and impaired clonogenic survival of glioma stem cells, but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protected glioma stem cells against radiation. Notch inhibition with GSIs did not alter the DNA damage response of glioma stem cells following radiation, but rather reduced Akt activity and Mcl-1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impaired xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment.
