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Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model.

Scientific reports (2016-11-17)
Doerte Poburski, Christiane Leovsky, Josefine Barbara Boerner, Luisa Szimmtenings, Michael Ristow, Michael Glei, René Thierbach

The increased cancer mortality of diabetes type 2 patients is most likely an evidence of the tight connection between tumor development and energy metabolism. A major focus of today's research is still the identification of key proteins of both diseases and the development of corresponding inhibitors. In this study we combined the two-stage BALB/c-3T3 cell transformation assay (BALB-CTA) with the IR/IGF-1R inhibitor OSI-906 (linsitinib) and analyzed alterations in protein activity and energy parameters in non-transformed as well as transformed cells. OSI-906 successfully inhibited the phosphorylation of IR/IGF-1R and decreased cell growth in non-transformed cells. In the BALB-CTA, a permanent treatment with OSI-906 reduced cellular transformation dose-dependently, whereas a temporary treatment gave evidence for a preventive effect in the promotion phase. Furthermore, even though several key proteins were affected, it was possible to show that the phosphorylation of GSK3, Erk 1/2 and the S6 protein are not crucial for the cell foci reducing effect of OSI-906. Taken together, the BALB-CTA confirmed results of OSI-906 from animal studies and enhanced the knowledge of its mode of action. Therefore, the BALB-CTA offers the opportunity to analyze alterations in the transformation process more precisely and will be helpful to identify effective cancer treatments.

Product Number
Product Description

Insulin solution from bovine pancreas, 10 mg/mL insulin in 25  mM HEPES, pH 8.2, BioReagent, sterile-filtered, suitable for cell culture
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
Tris(2-pyridylmethyl)amine, 98%