Abstract
The cytotoxic effect of 5-fluorouracil (5FU) and regorafenib (RF), drugs with different mechanisms of action used to treat colorectal cancer, on an HT29 cell line cultured on plastic or laminin 521 (LM-521) has been studied. It is first shown that LM-521 can increase the sensitivity of tumor cells to 5FU. A possible mechanism of the observed effect of LM-521 on the HT29 cell viability is proposed based on transcriptome and proteome analysis. The interaction of β1-containing integrins on the cell surface with LM-521 can activate the FAK/PI3K/Akt signaling pathways and promote phosphorylation of the YAP transcription coactivator and its binding to the complex with the 14-3-3σ protein. The formation of this complex leads to YAP retention in the cytoplasm and prevents its transport to the nucleus and the activation of antiapoptotic gene transcription.
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ACKNOWLEDGMENTS
The proteome analysis was carried out on the equipment of Human Proteome Center for Common Use (IBMKh).
Funding
The study was funded by the Russian Science Foundation (project no. 17-14-01338).
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Translated by I. Gordon
Abbreviations: DMSO—dimethyl sulfoxide; DPBS—Dulbecco’s phosphate-buffered saline; DTT—1,4-dithiotreitol; ECM—extracellular matrix; FBS—fetal bovine serum; 5FU—5-fluorouracil; IC50—half-maximal inhibition of cell viability; LM-521—laminin 521; MTT—3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide; OD—optical density; RF—regorafenib; RIN—RNA integrity number; TCEP—Tris-(2-carboxyethyl)phosphine.
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Raigorodskaya, M.P., Turchinovich, A., Tsypina, I.M. et al. Laminin 521 Modulates the Сytotoxic Effect of 5-Fluorouracil on HT29 Colorectal Cancer Cells. Appl Biochem Microbiol 56, 870–874 (2020). https://doi.org/10.1134/S0003683820080074
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DOI: https://doi.org/10.1134/S0003683820080074