Correlation of SERPINA-1 Gene Over-Expression with Inhibition of Cell Proliferation and Modulation of the Expression of IL-6, Furin, and NSD2 Genes

Background and objectives: IL-6 is a cytokine that promotes the proliferation of can-cer cells by activating the JAK/STAT pathway via STAT3, which is expressed after methylation by NSD2. Furin, a pro-protein convertase responsible for the maturation of several precursor proteins such as pro-IGF-1R, involved in the activation of PI3K/AKT and the MAPK pathway, plays a crucial role in cancer proliferation. Our objective is to observe the impact of the overexpression of SERPINA-1, an an-ti-inflammatory and serine protease inhibitor, on cell proliferation and the genetic ex-pression of IL-6, Furin, and NSD2. Materials and Methods: In hetero-hybrid lympho-blastoid cells either transfected with the SERPINA-1 gene (JP7pSer+) or without the SERPINA-1 gene (JP7pSer-); we studied by qRT-PCR the genetic overexpression of the SERPINA-1 gene and the genetic expression of Furin, IL-6, and NSD2 genes. Cell pro-liferation was tested by colorimetric and enzymatic methods, and the membrane ex-pression of IGF-1R was measured by flow cytometry. Results: The proliferation of the JP7pSer+ cell line is decreased by 91% and 85% in both measurement methods on day 6 compared to JP7pSer- cells. The kinetics of the genetic expression of Furin, IL-6, and NSD2 show an increase in expression times in JP7pSer+ cells compared to JP7pSer- cells, but after three days, this ratio is reversed. The ratio of mean fluorescence intensi-ty shows that JP7pSer- cells express 1.33 times more IGF-1R than JP7pSer+ cells. Con-clusion: These results suggest promising therapeutic avenues for cancer, which should be complemented by advanced studies on the expression of SERPINA-1 and the inter-action with the expression of IL-6 and Furin.