Sci Transl Med：患莱伦氏综合症为何不会患癌症和糖尿病

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

Changhan Lee1,*, Lizzia Raffaghello2,*, Sebastian Brandhorst1,5, Fernando M. Safdie1, Giovanna Bianchi2 , Alejandro Martin-Montalvo3, Vito Pistoia2, Min Wei1, Saewon Hwang1, Annalisa Merlino1, Laura Emionite4, Rafael de Cabo3 and Valter D. Longo1,†

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 (S. cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation (fasting) were as effective as chemotherapeutic agents in delaying progression of specific 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 toxic chemotherapy drugs in the treatment of various cancers.