Efeito da nicotina na expressão de HIF-1α, VEGF-A, FIH e PHD3 em linhagens celulares SCC-9 e DOK

Abstract

Oral Squamous Cell Carcinoma (OSCC) is considered a public health problem worldwide, with significant mortality and morbidity rates. The main risk factors for OSCC are smoking, alcoholism and HPV. Regarding tobacco, this is composed of more than 7000 substances among these nicotine, which contributes to the process of carcinogenesis. The contribution of nicotine to carcinogenesis is related to the activation of multiple signaling pathways that also regulate the progression, growth and metastasis of tumors through the stimulation of nicotinic acetylcholine receptors (nAChRs).Research has shown that exposure to nicotine may mimic the effects of hypoxia and promote positive regulation in the gene expression of pathway-related genes, such as HIF-1α, VEGF-A, FIH and PHD3.In order to observe the influence of nicotine on the gene expression of some proteins of the hypoxia pathway in oral cavity Oral Squamous Cell Carcinoma lines (SCC-9) and oral keratinocytes with dysplasia (DOK), was been realized analysis of cell viability and gene expression of the HIF-1α, VEGF-A, FIH and PHD3 genes by means of the MTS and RT-qPCR tests, respectively, and the calculations and statistical graphics performed by GraphPad Prism® v.7. It was observed that nicotine promotes cell proliferation in the SCC-9 line in a dose-dependent and time-dependent manner, with an 8h time. The same was not observed for DOK lines. In relation to nicotine gene expression it induces the expression of HIF-1α in SCC-9 and DOK cells in a dose-dependent and time-dependent manner and the expression of HIF-1α contributes, at least in part, to the expression of VEGF-A under induction of nicotine. It has also been observed that nicotine has a high inhibitory potential in the gene expression of FIH and PHD3 genes. Therefore, nicotine has a regulatory role in the hypoxia pathway that contributes to cell adhesion, invasion, migration and metastasis, suggesting that smoking or direct exposure to nicotine may be related to possible responses to treatment in patients with oral squamous cell carcinoma.