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Chenodeoxycholic acid inhibits lung adenocarcinoma progression via the integrin α5β1/FAK/p53 signaling pathway.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2022 May 15; Vol. 923, pp. 174925. Date of Electronic Publication: 2022 Mar 30. - Publication Year :
- 2022
-
Abstract
- Background: Lung cancer is the leading cause of cancer-associated death worldwide and is classified into non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC accounts for approximately 80%-85% of all lung cancer cases. Chenodeoxycholic acid (CDCA), a primary bile acid, has been reported to inhibit carcinoma cell proliferation. Here, we aimed to determine the effects and mechanism of action of CDCA against lung adenocarcinoma (LUAD).<br />Methods: Western blotting and quantitative real-time polymerase chain reaction were used to evaluate the protein and mRNA expression levels in LUAD cell lines, respectively. Cell Counting Kit-8 and clone formation assays were performed to evaluate the proliferation ability of different cell types in vitro. Tumor cell motility was evaluated using Transwell assays. The transcriptional profile of A549 cells treated with CDCA was determined through RNA sequencing analysis. A xenograft model was established to evaluate the effects of CDCA on LUAD progression in vivo.<br />Results: CDCA inhibited LUAD cell proliferation, migration, and invasion. Furthermore, it promoted apoptosis in LUAD cells. Mechanistically, CDCA inhibited the integrin α5β1 signaling pathway in LUAD cells by inhibiting the expression of the α5 and β1 subunits of integrin and phosphorylated FAK. Moreover, CDCA induced an increase in the levels of p53, a downstream gene of the integrin α5β1/FAK pathway. In addition, CDCA significantly decreased tumor volume in mice without inducing significant toxicity.<br />Conclusions: Our findings indicate that CDCA attenuates LUAD pathogenesis in vitro and in vivo via the integrin α5β1/FAK/p53 axis.<br /> (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Chenodeoxycholic Acid pharmacology
Chenodeoxycholic Acid therapeutic use
Focal Adhesion Kinase 1
Gene Expression Regulation, Neoplastic
Humans
Integrin alpha5beta1 metabolism
Mice
Tumor Suppressor Protein p53 metabolism
Adenocarcinoma of Lung genetics
Lung Neoplasms metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 923
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35364069
- Full Text :
- https://doi.org/10.1016/j.ejphar.2022.174925