Cytotoxic effect of metformin on butyrate-resistant PMF-K014 colorectal cancer spheroid cells - 03/06/22
Abstract |
Three-dimensional (3D) cell culture models are used in cancer research because they mimic physiological responses in vivo compared with two-dimensional (2D) culture systems. Recently, cross-resistance of butyrate-resistant (BR) cells and chemoresistance in colorectal cancer (CRC) cells have been reported; however, effective treatments for BR cells have not been identified. In this study, we investigated the cytotoxicity of metformin (MET), an anti-diabetic drug, on BR CRC cells in a 3D spheroid culture model. The results demonstrate that MET decreases spheroid size, migration, and spheroid viability, while it increases spheroid death. The molecular mechanism revealed that AMP-activated protein kinase (AMPK) and Akt serine/threonine kinase 1(Akt) were significantly upregulated, whereas the acetyl-CoA-carboxylase (ACC) and mammalian target of rapamycin (mTOR) were downregulated, which led to caspase activation and apoptosis. Our findings show the potential cytotoxicity of MET on CRC-BR cells. The combination of MET and conventional chemotherapeutic drugs should be addressed in further studies to reduce the side effects of standard chemotherapy for CRC.
El texto completo de este artículo está disponible en PDF.Graphical Abstract |
Highlights |
• | The proteome patterns of PMF-BR cells and their parental spheroids were compared. |
• | Differences among spheroids in pathway, biological process, and molecular function. |
• | PMF-BR spheroids were cross-resistant to 5-FU. |
• | Metformin treatment has a cytotoxic effect on PMF-BR cells and parental spheroids. |
Keywords : Colorectal cancer cell, Butyrate resistance, Metformin, Spheroid cell
Esquema
Vol 151
Artículo 113214- juillet 2022 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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