PT  - JOURNAL ARTICLE
AU  - Tao Liao
AU  - Xiao-Hui Li
AU  - Yan-Ping Chen
AU  - Li-Li Tan
AU  - Ji-Da Zhang
AU  - Xin-An Huang
AU  - Qin Xu
AU  - Sui-Qing Huang
AU  - Chang-Qing Li
AU  - Qing-Ping Zeng
TI  - Insulin Does Not Augment <em>In Vitro</em> Tumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner
AID  - 10.1101/169664
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 169664
4099  - http://biorxiv.org/content/early/2017/07/28/169664.short
4100  - http://biorxiv.org/content/early/2017/07/28/169664.full
AB  - Background Whether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).Methodology/Principle Findings We cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated by NOS2 knockdown.Conclusions/Significance Cellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.