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Sci. Transl. Med:禁食可使癌细胞对化疗更敏感

来源:生物谷 2012-03-10 20:18

近日,国际期刊Science Translational Medicine发表的一篇研究论文称,饮食限制(DR,dietary restriction)可以减慢肿瘤细胞的生长,并可使多种肿瘤对化疗药物更敏感。这项研究由美国、意大利和德国研究人员组成的国际研究小组共同完成。

短期饥饿能够保护正常细胞、小鼠免受大量化疗药物副作用的影响。减少卡路里或饮食限制20-40%就可以保护大量有机体免受氧化胁迫和衰老的影响。因此,理论上DR可以用于临床,避免化疗的副作用。然而,DR不适用于因癌症本身或者化疗已有体重减轻倾向的病人。动物实验结果证实,几个月的DR可以起到保护的作用。

研究人员发现,饥饿可使表达类癌基因RAS2val19的酵母细胞对氧化胁迫更加敏感。在17种哺乳动物癌细胞系中有15种可因饥饿对化疗药物更敏感。在神经母细胞瘤小鼠模型中,禁食和化疗药物共同作用可治愈小鼠的癌症。

为探讨引起这一现象的机制,研究人员认为或许是低浓度的细胞外葡萄糖和生长因子增加了肿瘤细胞中DNA的损伤。进一步的细胞水平实验发现,将葡萄糖和血清浓度降低到饥饿后的浓度,4T1乳腺癌细胞和B16黑色素瘤细胞中的DNA损伤与单独化疗相比都增加。

若临床实验也能达到预期效果,早期癌症病人或许可以不必冒化疗的风险,晚期癌症病人癌症复发的风险也可降低。(生物谷Bioon.com)

Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

Changhan Lee, Lizzia Raffaghello, Sebastian Brandhorst, Fernando M. Safdie, Giovanna Bianchi, Alejandro Martin-Montalvo, Vito Pistoia, Min Wei1, Saewon Hwang, Annalisa Merlino, Laura Emionite, Rafael de Cabo and Valter D. Longo

Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.

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