人们知道限制饮食对啮齿类动物有抗癌效果已有几十年了，但令人吃惊的是，我们对决定某种肿瘤是否会对节食措施产生反应的分子机制却知之甚少。
Nada Kalaany 和David Sabatini报告，某些人类癌细胞系，当在小鼠体内作为肿瘤异体移植物生长时，对于饮食限制的抗生长效应非常敏感，而人类的其他癌细胞系则对此有抵抗力。现在，造成肿瘤不同敏感度的原因，已被发现是“phosphatidylinositol-3-kinase (PI3K)/Akt”信号通道的活化状态。因此，这一通道的状态可能是指示哪些肿瘤会对模仿饮食限制的治疗方法产生反应的一个指示器。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 458, 725-731 (9 April 2009) | doi:10.1038/nature07782
Tumours with PI3K activation are resistant to dietary restriction
Nada Y. Kalaany1,2,3 & David M. Sabatini1,2,3,4
1 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
2 Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3 Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
4 Broad Institute, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA
AbstractDietary restriction delays the incidence and decreases the growth of various types of tumours, but the mechanisms underlying the sensitivity of tumours to food restriction remain unknown. Here we show that certain human cancer cell lines, when grown as tumour xenografts in mice, are highly sensitive to the anti-growth effects of dietary restriction, whereas others are resistant. Cancer cells that form dietary-restriction-resistant tumours carry mutations that cause constitutive activation of the phosphatidylinositol-3-kinase (PI3K) pathway and in culture proliferate in the absence of insulin or insulin-like growth factor 1. Substitution of an activated mutant allele of PI3K with wild-type PI3K in otherwise isogenic cancer cells, or the restoration of PTEN expression in a PTEN-null cancer cell line, is sufficient to convert a dietary-restriction-resistant tumour into one that is dietary-restriction-sensitive. Dietary restriction does not affect a PTEN-null mouse model of prostate cancer, but it significantly decreases tumour burden in a mouse model of lung cancer lacking constitutive PI3K signalling. Thus, the PI3K pathway is an important determinant of the sensitivity of tumours to dietary restriction, and activating mutations in the pathway may influence the response of cancers to dietary restriction-mimetic therapies.
