Effect Of VPA and TGF-β on epithelial to mesenchymal transition in lung cancer

Abstract

Lung cancer is the one of the most diagnosed cancer in the world, as well as the leading cause of death amongst cancer patients. Epithelial to mesenchymal transition (EMT) is the process by which epithelial cells acquire a mesenchymal phenotype, gaining characteristics such as increased migratory capacity, invasiveness, and resistance to treatment. This process is important in cancer as it enables tumour cells to become more mobile and invasive, leading to metastasis. The main aim of this thesis was to investigate how two molecules; valproic acid (VPA) and transforming growth factor-β (TGF-β) affect epithelial–mesenchymal transition (EMT) in lung cancer cells, specifically in H460 cells, which are classified as large cell lung cancer (LCLC) cells. VPA is a histone deacetylase inhibitor (HDACI), which has been shown to either inhibit or activate EMT based on the specific cell line and concentration. TGF-β plays an important role in cell proliferation, differentiation, and wound healing. Cell proliferation and cytotoxicity of VPA and TGF-β were tested on H460 cells by MTT assays. Moreover, gene analysis of mesenchymal biomarkers including FN1, SNAI1, VIM, and ZEB1 was carried out on cells treated with VPA. Results showed that both these molecules demonstrated a dose-dependent influence on H460 cell viability, as they both exerted a cytotoxic effect at higher concentrations. Gene expression analysis showed that VPA treatment affects EMT markers in a time and dose dependent manner, where mesenchymal markers were downregulated at earlier time-points, and generally upregulated at a higher concentration and later time-points. Further work includes performing mesenchymal-associated gene expression analysis on TGF-β-treated cells.