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雷帕霉素可延长杂合型p53+/-小鼠的寿命并延缓其肿瘤发生。

Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/- mice.

作者信息

Komarova Elena A, Antoch Marina P, Novototskaya Liliya R, Chernova Olga B, Paszkiewicz Geraldine, Leontieva Olga V, Blagosklonny Mikhail V, Gudkov Andrei V

机构信息

Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

出版信息

Aging (Albany NY). 2012 Oct;4(10):709-14. doi: 10.18632/aging.100498.

Abstract

TOR (Target of Rapamycin) pathway accelerates cellular and organismal aging. Similar to rapamycin, p53 can inhibit the mTOR pathway in some mammalian cells. Mice lacking one copy of p53 (p53+/- mice) have an increased cancer incidence and a shorter lifespan. We hypothesize that rapamycin can delay cancer in heterozygous p53+/- mice. Here we show that rapamycin (given in a drinking water) extended the mean lifespan of p53+/- mice by 10% and when treatment started early in life (at the age less than 5 months) by 28%. In addition, rapamycin decreased the incidence of spontaneous tumors. This observation may have applications in management of Li-Fraumeni syndrome patients characterized by heterozygous mutations in the p53 gene.

摘要

雷帕霉素靶蛋白(TOR)信号通路会加速细胞和机体衰老。与雷帕霉素类似,p53在某些哺乳动物细胞中可抑制mTOR信号通路。缺失一个p53拷贝的小鼠(p53+/-小鼠)癌症发病率增加且寿命缩短。我们推测雷帕霉素可延缓杂合p53+/-小鼠患癌。在此我们表明,雷帕霉素(通过饮用水给予)使p53+/-小鼠的平均寿命延长了10%,若在生命早期(小于5个月龄)开始治疗则延长了28%。此外,雷帕霉素降低了自发肿瘤的发生率。这一观察结果可能对以p53基因杂合突变为特征的李-佛美尼综合征患者的治疗有应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69ac/3517941/50640947e329/aging-04-709-g001.jpg

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