Chenodeoxycholic acid inhibits lung adenocarcinoma progression via the integrin α5β1/FAK/p53 signaling pathway

• DOI: 10.1016/j.ejphar.2022.174925
• Publication Date: 2022-03-30T00:38:53Z
• Authors: Dan Shen; Yuanyuan Zeng; Weijie Zhang; Yue Li; Jianjie Zhu; Zeyi Liu; Zhaowei Yan; Jian-an Huang
• Keywords: 0303 health sciences; Lung Neoplasms; Adenocarcinoma of Lung; Chenodeoxycholic Acid; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Focal Adhesion Kinase 1; Animals; Humans; Tumor Suppressor Protein p53; Cell Proliferation; Integrin alpha5beta1; Signal Transduction

Lung cancer is the leading cause of cancer-associated death worldwide and classified into non-small cell lung (NSCLC) small-cell (SCLC). NSCLC accounts for approximately 80%-85% all cases. Chenodeoxycholic acid (CDCA), a primary bile acid, has been reported to inhibit carcinoma proliferation. Here, we aimed determine effects mechanism action CDCA against adenocarcinoma (LUAD).Western blotting quantitative real-time polymerase chain reaction were used evaluate protein mRNA expression levels in LUAD lines, respectively. Cell Counting Kit-8 clone formation assays performed proliferation ability different types vitro. Tumor motility was evaluated using Transwell assays. The transcriptional profile A549 cells treated with determined through RNA sequencing analysis. A xenograft model established on progression vivo.CDCA inhibited proliferation, migration, invasion. Furthermore, it promoted apoptosis cells. Mechanistically, integrin α5β1 signaling pathway by inhibiting α5 β1 subunits phosphorylated FAK. Moreover, induced an increase p53, downstream gene α5β1/FAK pathway. In addition, significantly decreased tumor volume mice without inducing significant toxicity.Our findings indicate that attenuates pathogenesis vitro vivo via α5β1/FAK/p53 axis.