Nature：抗氧化剂在某些条件下有利于癌细胞存活

niyou

来自试管研究和动物研究的实验证据表明，抗氧化剂也许能抑制癌症形成，尽管有关其在临床条件下的效果还几乎没有结论性证据。然而，发现在某些条件下抗氧化剂能帮助促进癌细胞存活和增殖却有点儿出乎意料。- i" ~$ g/ v6 Z5 E' m$ _
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正常表皮细胞如果与在结构上具有支持作用的细胞外基质脱离时就会死亡，但在乳腺癌中，引起癌症的基因如erbB2能为脱离的肿瘤发生细胞提供存活信号。) @: c9 t9 L6 g, D( k6 R5 _
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Schafer等人发现，细胞脱离还会引起代谢缺陷，这些缺陷被erbB2和被抗氧化剂都可挽救，抗氧化剂似乎是通过经由脂肪酸氧化提升细胞能量水平来发挥作用的。这些发现指出了一些新的机制，它们有可能被癌细胞利用，来增强自己在被改变的基质环境中的存活能力。
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原始出处：
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6 U" e7 L* f" U# z5 M* ANature 461, 109-113 (3 September 2009) | doi:10.1038/nature08268
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Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment, e, Y; }) A* ?  k6 Y

% V, R6 e6 |& U( m. r+ V7 u  LZachary T. Schafer1,4, Alexandra R. Grassian1,5, Loling Song1,5, Zhenyang Jiang1, Zachary Gerhart-Hines2,3, Hanna Y. Irie1, Sizhen Gao1, Pere Puigserver1,2 & Joan S. Brugge1
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2 ]& p' c+ t. c" D# `1 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
3 {2 I% ?+ O& [' d- b. z2 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; q- M9 |0 J8 v2 x& E! B0 U
3 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
7 w; ~& c. Y6 r) j& H8 F6 z& v4 Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
& K+ x4 ^9 ?  n! u, Z. x* S5 These authors contributed equally to this work.: u8 v! u9 U% G5 ^: u8 b# H

4 y+ {6 B$ K) CNormal epithelial cells require matrix attachment for survival, and the ability of tumour cells to survive outside their natural extracellular matrix (ECM) niches is dependent on acquisition of anchorage independence1. Although apoptosis is the most rapid mechanism for eliminating cells lacking appropriate ECM attachment2, recent reports suggest that non-apoptotic death processes prevent survival when apoptosis is inhibited in matrix-deprived cells3, 4. Here we demonstrate that detachment of mammary epithelial cells from ECM causes an ATP deficiency owing to the loss of glucose transport. Overexpression of ERBB2 rescues the ATP deficiency by restoring glucose uptake through stabilization of EGFR and phosphatidylinositol-3-OH kinase (PI(3)K) activation, and this rescue is dependent on glucose-stimulated flux through the antioxidant-generating pentose phosphate pathway. Notably, we found that the ATP deficiency could be rescued by antioxidant treatment without rescue of glucose uptake. This rescue was found to be dependent on stimulation of fatty acid oxidation, which is inhibited by detachment-induced reactive oxygen species (ROS). The significance of these findings was supported by evidence of an increase in ROS in matrix-deprived cells in the luminal space of mammary acini, and the discovery that antioxidants facilitate the survival of these cells and enhance anchorage-independent colony formation. These results show both the importance of matrix attachment in regulating metabolic activity and an unanticipated mechanism for cell survival in altered matrix environments by antioxidant restoration of ATP generation.

上海过客

这个 对 我们的研究  可真是一个打击啊 ; Y% _6 _, n) T  |2 M  d

+ k, Z) Z) X$ T' N7 o; b+ V我们就是研究 抗氧化的  。

syapxlg

科学就是悖论，没有绝对的东西，也许科学的魅力在于不断的自我超越，破除常识，头脑中的禁锢！

llingzu

也许吧