PLoS ONE：禁食让脑瘤对化疗更加敏感

在一项新研究中，来自美国南加州大学的研究人员首次证实控制性禁食(controlled fasting)改善在癌症治疗中的化疗疗效，延长患有侵袭性脑瘤的小鼠的预期寿命。

在这项刊登在PLoS ONE期刊上的最新研究中，研究人员首次证实禁食时间似乎提高化疗在治疗神经胶质瘤上的疗效。神经胶质瘤是一种最为常见被诊断出来的脑瘤。患有神经胶质瘤的病人平均存活期限小于两年。

论文通信作者Valter Longo和他的同事们研究了禁食与化疗以及禁食与化疗药物替莫唑胺(Temozolomide)组合使用的疗效。他们发现对小鼠进行控制性短期禁食，每个治疗周期不超过48个小时，能够改善化疗和化疗在治疗神经胶质瘤中的疗效。即便所研究的脑瘤能够极其侵袭性地生长，参加禁食和接受化疗治疗的小鼠在治疗结束时存活的数量是只参加禁食或只接受化疗治疗的那些小鼠的两倍多。

这些研究结果证实禁食和标准化疗与放疗在治疗神经胶质瘤中发挥出有益性作用。

Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy

Fernando Safdie1#, Sebastian Brandhorst1,4#, Min Wei1, Weijun Wang2, Changhan Lee1, Saewon Hwang1, Peter S. Conti3, Thomas C. Chen2, Valter D. Longo

Background
Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.
Methodology and Principal Findings
To test the effect of starvation on glioma cells in vitro, we treated primary mouse glia, murine GL26, rat C6 and human U251, LN229 and A172 glioma cells with Temozolomide in ad lib and STS mimicking conditions. In vivo, mice with subcutaneous or intracranial models of GL26 glioma were starved for 48 hours prior to radio- or chemotherapy and the effects on tumor progression and survival were measured. Starvation-mimicking conditions sensitized murine, rat and human glioma cells, but not primary mixed glia, to chemotherapy. In vivo, starvation for 48 hours, which causes a significant reduction in blood glucose and circulating insulin-like growth factor 1 (IGF-1) levels, sensitized both subcutaneous and intracranial glioma models to radio-and chemotherapy.
Conclusion
Starvation-induced cancer sensitization to radio- or chemotherapy leads to extended survival in the in vivo glioma models tested. These results indicate that fasting and fasting-mimicking interventions could enhance the efficacy of existing cancer treatments against aggressive glioma in patients.