杜克大學醫(yī)學中心的研究人員指出,，在致命的腦癌中,，干細胞對放療更具抑制效果,。而在實驗室中,，通過對這些癌癥干細胞使用一種藥物阻斷一個特殊的信號通路，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)瘤細胞,。
這項研究是在早期研究的基礎(chǔ)上進行的。之前的研究表明癌癥干細胞抑制放療的效果比其他癌細胞更強,。
杜克大學的研究人員識別了一種信號通路,，該通路叫Notch，其是抑制效果增強的潛在原因,。Notch同樣在正常的干細胞中存在,，對細胞之間的交流很重要。這項研究結(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,。這項研究的負責人Jialiang Wang博士介紹說，Notch通路可以作為一個有前途的藥物靶標,，開發(fā)出正確的藥物或能阻止真正的有害“家伙”-神經(jīng)膠質(zhì)瘤干細胞,。
癌癥中的干細胞是癌細胞增殖的來源。數(shù)百個的癌癥干細胞能夠快速變成百萬的腫瘤細胞,。
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。在這項研究中,，該抑制劑單獨使用只是適度的降低了腫瘤細胞的生長,，但是在結(jié)合了臨床的放射療法后，會引起腫瘤組織中大量的細胞死亡,，并顯著降低了神經(jīng)膠質(zhì)瘤干細胞的生存,。因此聯(lián)合療法大大增強了對腫瘤細胞生長的抑制。（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.
