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Research in recent years revealed that the antidiabetic drug metformin has some anticancer properties, and p53 plays an important role in the metformin-induced tumor inhibition. But less clear is the mechanism by which p53 status affects metformin mediated cancer cell responses. In this study, the effect of metformin on cancer cells with different p53 genotypes was investigated, and we found metformin could inhibit cancer cell proliferation especially in p53-deficient cells. So a paired isogenic nonsmall cell lung cancer cell lines H1299 p53+/+ and H1299 p53-/was involved to explore the possible mechanisms. We detected the differences in cell proliferation and solid tumor formation induced by metformin, furthermore, the signaling transduction of insulin like growth factor-1 receptor (IGF-1R) was evaluated, which was essential in cancer transformation and progression. Our results indicated that p53 deficiency lead to more efficient inhibition of IGF-1R signaling transduction, receptor degradation and ubiquitination induced by metformin, which resulted in enhanced cell apoptosis and proliferation inhibition in vitro, and more significant solid tumor growth retardation and cancer cell death in vivo. Although more cell lines and multiple experiments were required to make a general conclusion, our study suggested the enhanced inhibition of IGF-1R signaling pathway contribute to the metformin’s selective toxicity in p53deficient lung adenocarcinoma cells.

WITHDRAWN: p53 deficiency resulted in enhanced IGF-1R signaling pathway inhibition by metformin in lung adenocarcinoma cells