Regulatory roles of ACSL5 in anti-tumor function of Palmitic acid (C16:0) via ERK signaling pathway

Abstract

Abstract Background Non-small cell lung cancer (NSCLC), accounting for 85% of all types of lung cancer cases, is a malignant disease with high incidence worldwide. Meanwhile, mounting evidence indicates this lesion is easily susceptible to the perturbation of lipids metabolism. Our team identified palmic acid (C16:0) as a novel treatment to interact with NSCLC for the first time and the expression patterns of ACSL5 stimulated by C16:0, however, its pathogenesis remains poorly understood in NSCLC. Methods A549 cells were treated with a different dose of palmitic acid. Then, CCK-8 assay, annexin V-FITC/PI double staining assay, wound healing assay and Transwell assay were performed to evaluate the effects of PA on proliferation, apoptosis, migration and invasion of A549 cells. Further, the expression levels of ACSL5 and the related proteins were detected by qPCR and Western blotting. Tumor volume assay and hematoxylin-eosin staining were used to detect tumor growth in vivo. Results The trend toward proliferation, apoptosis, migration and invasion can be substantially flattened by PA in A549 cells. Meanwhile, compared with the control group, a significant increase in expression levels of ACSL5 and related proteins has been observed in PA-treated A549 cells. Moreover, the knockdown of ACSL5 reversed the anti-tumor effect, resulting in an increase in the rate of above malignant phenotype in tumor. In addition, the expression of ERK phosphorylated protein was inhibited dramatically with the increased concentration of C16:0 in A549 cells. Conclusion C16:0 decreases the rate of proliferation and apoptosis, inhibits cell migration and invasion of NSCLC cells, and its mechanism may be related to the targeted regulation of ACSL5 and activation of the ERK pathway.