近日,，國(guó)際期刊Science Translational Medicine發(fā)表的一篇研究論文稱，飲食限制（DR,dietary restriction）可以減慢腫瘤細(xì)胞的生長(zhǎng),，并可使多種腫瘤對(duì)化療藥物更敏感,。這項(xiàng)研究由美國(guó)、意大利和德國(guó)研究人員組成的國(guó)際研究小組共同完成,。
短期饑餓能夠保護(hù)正常細(xì)胞,、小鼠免受大量化療藥物副作用的影響。減少卡路里或飲食限制20-40%就可以保護(hù)大量有機(jī)體免受氧化脅迫和衰老的影響,。因此,，理論上DR可以用于臨床，避免化療的副作用,。然而,，DR不適用于因癌癥本身或者化療已有體重減輕傾向的病人。動(dòng)物實(shí)驗(yàn)結(jié)果證實(shí),，幾個(gè)月的DR可以起到保護(hù)的作用,。
研究人員發(fā)現(xiàn)，饑餓可使表達(dá)類癌基因RAS2val19的酵母細(xì)胞對(duì)氧化脅迫更加敏感,。在17種哺乳動(dòng)物癌細(xì)胞系中有15種可因饑餓對(duì)化療藥物更敏感,。在神經(jīng)母細(xì)胞瘤小鼠模型中，禁食和化療藥物共同作用可治愈小鼠的癌癥,。
為探討引起這一現(xiàn)象的機(jī)制,，研究人員認(rèn)為或許是低濃度的細(xì)胞外葡萄糖和生長(zhǎng)因子增加了腫瘤細(xì)胞中DNA的損傷。進(jìn)一步的細(xì)胞水平實(shí)驗(yàn)發(fā)現(xiàn),，將葡萄糖和血清濃度降低到饑餓后的濃度,，4T1乳腺癌細(xì)胞和B16黑色素瘤細(xì)胞中的DNA損傷與單獨(dú)化療相比都增加。
若臨床實(shí)驗(yàn)也能達(dá)到預(yù)期效果,，早期癌癥病人或許可以不必冒化療的風(fēng)險(xiǎn),，晚期癌癥病人癌癥復(fù)發(fā)的風(fēng)險(xiǎn)也可降低。（生物谷Bioon.com）
doi:10.1126/scitranslmed.3003293
PMC:
PMID:
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.
