Exogenous interleukin-1α signaling negatively impacts acquired chemoresistance and alters cell adhesion molecule expression pattern in colorectal carcinoma cells HCT116

•Exogenous IL-1α-pretreated HCT116 cells are more sensitive to 5-fluorouracil (5-FU).•IL-1α-pretreatment also increases chemosensitivity of a 5-FU-resistant HCT116 cells.•Endogenous IL-1α impacts chemosensitivity only in the parental HCT116 cell line.•Both 5-FU and IL-1α treatments alter gene expres...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2019-02, Vol.114, p.38-46
Main Authors: Grigaitis, Pranas, Jonusiene, Violeta, Zitkute, Vilmante, Dapkunas, Justas, Dabkeviciene, Daiva, Sasnauskiene, Ausra
Format: Article
Language:English
Subjects:
Acquired chemoresistance
Apoptosis - drug effects
Apoptosis - genetics
Cell adhesion
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Cycle Checkpoints - drug effects
Cell Cycle Checkpoints - genetics
Cell death
Cell Shape - drug effects
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Down-Regulation - drug effects
Down-Regulation - genetics
Drug Resistance, Neoplasm - drug effects
Drug Resistance, Neoplasm - genetics
Fluorouracil - pharmacology
Gene Expression Regulation, Neoplastic - drug effects
Gene Ontology
HCT116 Cells
Humans
Interleukin-1alpha - metabolism
Interleukin-1α
Protein Interaction Maps
Recombinant Proteins - pharmacology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction - drug effects
Up-Regulation - drug effects
Up-Regulation - genetics
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Summary:•Exogenous IL-1α-pretreated HCT116 cells are more sensitive to 5-fluorouracil (5-FU).•IL-1α-pretreatment also increases chemosensitivity of a 5-FU-resistant HCT116 cells.•Endogenous IL-1α impacts chemosensitivity only in the parental HCT116 cell line.•Both 5-FU and IL-1α treatments alter gene expression of cell adhesion molecules. Proinflammatory cytokine and chemokine signaling from the tumor microenvironment is thought to be crucial for developing and sustaining colorectal cancer by regulating a multitude of pathways associated with a variety of cellular mechanisms. Among these pathways there is acquired chemoresistance, which is usually a major obstacle in the way towards successful chemotherapeutic treatment of advanced colorectal cancer cases. Despite of an emerging body of data published on the role of cytokine signaling network in cancer, little is known about the effects of the upstream cytokine interleukin-1α (IL-1α) signaling to the cancer cells. In this study we have shown that the increase in exogenous IL-1α signaling increases chemosensitivity of both chemosensitive and chemoresistant colorectal cancer cell lines, treated with a widely used cytotoxic antimetabolite 5-fluorouracil (5-FU). This was a result of increased cell death but not of the changes in 5-FU-induced cell cycle arrest. Noticeably, combined exogenous IL-1α and 5-FU treatment had significant effects on the expression of cell adhesion molecules, suggesting a decrease in adhesion-dependent chemoresistance and, on the other hand, an increase in metastatic potential of the cells. These results lead to a conclusion that modulation of IL-1 receptor activity could have applications as a part of combination therapy for advanced and highly metastatic colorectal cancers.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2018.11.031