The effect of valproic acid on lung cancer cell lines

Abstract

Epithelial-mesenchymal transition (EMT) plays an important role in lung cancer metastasis. During EMT, epithelial cells lose their polarity and cell-to-cell adhesion, becoming more invasive and mobile. EMT can be triggered by several inducers, including transforming growth factor beta (TGF-β) and histone deacetylase (HDAC) inhibitors like valproic acid (VPA). This study aimed to investigate the effect of VPA on EMT-related gene expression in two non-small cell lung cancer (NSCLC) cell lines: A549 and H1975. MTT assays were performed to identify the optimal seeding density, appropriate foetal bovine serum (FBS) conditions, and ideal VPA concentrations that maintained adequate cell viability without causing cytotoxicity. RNA was then extracted from cells treated with different doses of VPA (1.25 nM, 2.5 nM, and 5 nM) at 24 and 48 hours, and qPCR was carried out to measure changes in the expression of key epithelial and mesenchymal markers. The results showed a consistent upregulation of mesenchymal markers ZEB1 and SNAI1 in both cell lines, particularly after 48 hours, while epithelial markers CDH1 and EpCAM were mostly downregulated. In conclusion, VPA appears to enhance EMT in NSCLC cells by upregulating key transcription factors, with effects depending on concentration, time, and cell line. These results highlight the complexity and context-dependent nature of HDAC inhibitor activity and underscore the need for further research using longer time points, additional EMT markers, and protein-level validation to fully understand VPA’s role in EMT regulation.