Metformin exerts an antitumoral effect on papillary thyroid cancer cells through altered cell energy metabolism and sensitized by BACH1 depletion
Abstract
PURPOSE: Aberrant cell energy metabolism is one of the features of thyroid carcinogenesis. Metformin may reduce the risk of cancer, and BACH1 was reported to affect the sensitivity of cancer cells to metformin. The aims of this study were to investigate whether metformin exerts antitumor effects in PTC cells and explore the role of BACH1 depletion on the sensitivity of PTC cells to metformin.
METHODS: The viability and proliferation of PTC cell lines were analyzed with MTT and colony forming assay. Energy utilization and mitochondrial respiration were measured using Seahorse XF instruments and Mitochondrial complex-1 activity assay.
RESULTS: Our results showed the anti-proliferative and pro-apoptotic effects of metformin in PTC cells. Furthermore, metformin changed the pattern of cell energy metabolism in PTC cells, which manifested as inhibition of mitochondrial respiration, and the combination of BACH1 depletion with metformin magnified the effect of metformin alone.
CONCLUSIONS: In conclusion, metformin exerts an antitumoral effect on PTC cells both in vitro and in xenograft mouse models. A possible mechanism is through inhibiting glucose metabolism and mitochondrial respiration process. Knocking down BACH1 caused the switching of energy metabolism and sensitized PTC cells to metformin, which eventually enhanced the anti-tumor effect of metformin.
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