Comparative proteomic analysis of differentially expressed proteins in metastatic breast cancer cell lines in response to oral hypoglycemic treatment
Although the anti-cancer properties of metformin have been well studied and it is now well known that metformin acts on cell metabolism and suppresses breast cancer cell proliferation by a number of different mechanisms. Our study was designed to evaluate the effect of the clinical (0.3mM) and the potential tissue accumulation (5mM) doses of metformin using the global proteomic profiling. The similarity and differences of protein expression between the wild-type MDA-MB-231 (PCC) cell-line and its bone-homed (BM) and lung-homed (LM) variants were explored using the Spike-in SILAC proteomic techniques. The proteomic data suggest that metformin inhibits the expression of proteins within key cellular pathways in both triple negative breast cancer and the bone and lung homed variants, with the lung-homed cells showing a greater response to metformin treatment. We have demonstrated for the first time, that clinical- and potential tissue-relevant doses of metformin are associated with a number of significant proteomic changes, including the previously unreported changes in TNFAIP8, GRB2, STAT3, TSPO and calmodulin proteins in TNBC cells as well as their aggressive lung and bone homing metastatic variants, observed under our in vitro conditions. Taken together these data provide important novel insight into the useful role of metformin in breast cancer treatment, but further research is certainly required to identify biomarkers of response and mechanisms of action in breast cancer before metformin can be recommended in clinical practice.
Copyright (c) 2021 Aesha Bojazyah
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