Borger Darrell R, Gavrilescu L Cristina, Bucur Maria C, Ivan Mircea, Decaprio James A
Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Mayer Building 440, 44 Binney Street, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 2008 May 30;370(2):230-4. doi: 10.1016/j.bbrc.2008.03.056. Epub 2008 Mar 24.
This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen.
本研究旨在探究癌细胞在长期缺氧应激下的存活情况。采用了两个与致癌作用相关的系统：完全转化的BJ细胞和一种肾癌细胞系（786-0）。AMPK活性的动态变化与慢性缺氧期间的促存活作用一致。AMPK激动剂和拮抗剂（AICAR和化合物C）的作用进一步支持了这一点。显性负性AMPKα的表达导致ATP水平降低，并显著损害缺氧条件下的细胞存活。雷帕霉素的剂量依赖性促存活作用与mTOR抑制作为持续性低氧中AMPK的关键下游介质一致。
