Current research supports a strong link between obesity, type-2 diabetes, metabolic syndrome and cancer – related mortality. The link is attributed to increased insulin levels in the blood which in turn results in higher levels of the free bioactive growth hormone, Insulin-like growth factor 1 (IGF-1), which is a potent growth factor that induces cell proliferation and is present in many types of cancers. Through activation of the phosphatidylinositol 3-kinase (PI3K)-Akt/mTOR pathway, IGF-1R signaling also inhibits apoptosis. Mammalian target of rapamycin (mTOR) inhibition-induced apoptosis is prevented by the presence of IGF-1. We investigated the potential of concomitant inhibition of the IGF-1receptor and mTOR as a potential therapeutic strategy for growth inhibition and restoration of apoptosis in two pancreatic cancer cell lines. The cells were treated with an inhibitor of the kinase domain of IGF-1R, and an inhibitor of mTORC1. Using results of optimal drug concentrations that induced 50% of inhibitory cell growth (IC50) obtained in preliminary experiments, the cells were subjected to drug treatment followed by Western analysis of cell lysates. Results show that in all cell lines, cell growth inhibition and apoptosis is significantly higher in cell populations that received combination treatments.

Effect of PI3K-Akt/mTOR pathway inhibition on cell growth and apoptosis in Mia PaCa and PANC pancreatic cancer cell lines

251st National Meeting (2016)

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