EFFECT OF NICOTINE ON HIF-1α EXPRESSION,
VEGF-A, FIH AND PHD3 IN CELLULAR LINES
SCC-9 AND DOK
Name: MAYARA MOTA DE OLIVEIRA
Publication date: 23/02/2017
Advisor:
Name |
Role |
|---|---|
| ADRIANA MADEIRA ALVARES DA SILVA | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ADRIANA MADEIRA ALVARES DA SILVA | Advisor * |
| LEONARDO OLIVEIRA TRIVILIN | Internal Examiner * |
Summary: OLIVEIRA, M.M. EFEITO DA NICOTINA NA EXPRESSÃO DE HIF-1α, VEGF-A,
FIH E PHD3 EM LINHAGENS CELULARES SCC-9 E DOK, 2017, 60f. Dissertação
de Mestrado Universidade Federal do Espírito Santo.
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.
Key words: oral squamous cell carcinoma. smoking. nicotine. hypoxia. RT-
qPCR.
