Nicotine exposure increases PIK3CA, AKT1, HIF-1α, GLUT1, CA9 and VEGF expression in oral potentially malignant lesions

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy often arising from oral potentially malignant lesions (OPMD). Nicotine triggers pathways associated with tumor progression, angiogenesis, and metastasis, notably PI3K/AKT and HIF-1. This study investigated the impact of nicotine on cell viability, migration, and gene expression (PIK3CA, AKT1, HIF-1α, GLUT1, CA9 and VEGF) in DOK and SCC9 cell lines. Methods and Results: DOK and SCC9 cell lines, were cultured in standard media and conditions, exposed to different nicotine concentrations (control, 1 µM, and 10 µM) for 8 and 24 hours. Cell viability assay, wound healing scratch assay cell, RNA extraction and RT-qPCR analysis of target genes were performed. Nicotine increased DOK cell migration and mRNA expression of PIK3CA, AKT1, HIF-1α, GLUT1, CA9, and VEGF after 8-hour exposure to 10 µM nicotine. Conclusions Our results suggest a relationship between nicotine exposure and the increased expression of genes that have a strict association with metabolites, survival, proliferation and inhibition of apoptosis in DOK, where the expression patterns were well-defined within 8 hours and in a dose-dependent manner. Further studies are warranted to comprehend nicotine's intricate mechanisms impacting oral cancer progression.