Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells.
Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells.
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DOI：
10.1002/cbf.1541
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发表时间：
2009-03
影响因子：
3.6
通讯作者：
Ayene, Iraimoudi S.
中科院分区：
文献类型：
--
作者：
Li, Jie;Ayene, Roashan;Ward, Kathleen M.;Dayanandam, Eswarkumar;Ayene, Iraimoudi S.
最近的研究表明，营养缺乏，特别是葡萄糖，可能在肿瘤细胞耐受实体瘤中的一般氧化应激环境中发挥重要作用。本文研究了葡萄糖剥夺对人结肠癌细胞（HT 29）0020和前列腺癌细胞（DU 145）γ辐射反应的影响。通过生物还原测定，在葡萄糖剥夺的细胞中观察到细胞内葡萄糖水平的显著降低。在无葡萄糖条件下，HT 29和DU 145细胞经γ射线照射后的存活率分别比有葡萄糖条件下提高30%和100%。在去糖培养液中，自由基清除剂谷胱甘肽（GSH）含量保持不变，与去糖诱导的辐射抗性无相关性。GRP 78是一种应激反应存活蛋白，与葡萄糖中的细胞相比，在葡萄糖剥夺4小时的细胞中没有显著增加。已知DNA修复蛋白Ku在细胞对辐射的抗性中起主要作用，其在显示增强的辐射抗性的葡萄糖剥夺癌细胞中显著增加。这些结果首次证明，葡萄糖剥夺介导的应激增加了人癌细胞中核Ku的表达和对辐射诱导的氧化应激的抗性。由于扩散限制的血液供应和较高的代谢活性，已知实体瘤具有低水平的葡萄糖，因此由癌细胞中的葡萄糖剥夺引起的额外抗性具有临床意义。
Recent studies have indicated that nutrient deprivation particularly glucose may play a major role in tumor cell tolerance to a generally oxidative stress environment in solid tumors. Here, we studied the impact of glucose deprivation on the response of human colon (HT29)0020and prostate (DU145) cancer cells to γ radiation. A significant decrease in intracellular glucose level was observed in glucose deprived cells as measured by bioreductive assay. The survival of HT29 and DU145 were increased by 30 and 100% respectively when these cells were exposed to γ radiation in the absence of glucose compared to that in the presence of glucose. In glucose depleted medium, glutathione (GSH), a free radical scavenger, content remained the same, and showed no correlation with the radiation resistance induced by glucose deprivation. GRP78, a stress response survival protein, was not significantly increased in cells deprived of glucose for 4 hours compared to those cells in glucose. DNA repair protein Ku, which is known to play a major role in cellular resistance to radiation, was significantly increased in glucose deprived cancer cells that showed enhanced radiation resistance. These results have demonstrated, for the first time, that glucose deprivation mediated stress increased the expression of nuclear Ku and resistance to radiation induced oxidative stress in human cancer cells. The additional resistance caused by glucose deprivation in cancer cells has clinical significance since solid tumors are known to have low level of glucose due to diffusion limited blood supply and higher metabolic activity.
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影响因子：
11.2
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E
通讯作者：
Sivridis, E
影响因子：
3.1
作者：
DeLeve, LD;Wang, XD
通讯作者：
Wang, XD
影响因子：
4.8
作者：
Ayene, IS;Stamato, TD;Koch, CJ
通讯作者：
Koch, CJ
影响因子：
4
作者：
Ayene, Iraimoudi S.;Biaglow, John E.;Koch, Cameron J.
通讯作者：
Koch, Cameron J.
影响因子：
3.4
作者：
Geng, L;Walter, S;Vaughan, ATM
通讯作者：
Vaughan, ATM