TITLE:
Simvastatin Action Is Not Related to HDAC2 Expression in Non-Small Cell Lung Cancer (NSCLC)
AUTHORS:
Gallelli Luca, Falcone Daniela, Perri Mariarita, Erika Cione, Pelaia Girolamo, Mesuraca Maria, Terracciano Rosa, Spaziano Giuseppe, D’Agostino Bruno, Navarra Michele, Savino Rocco
KEYWORDS:
Lung Adenocarcinoma Cells, HDAC2, Statins, Cell Proliferation, Cytokines
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.12,
November
17,
2016
ABSTRACT: In this study, we lowered the expression of HDAC2
protein, to evaluate the effects of simvastatin on the biochemical pathways
involved in inflammatory and metastatic response. The model used is the
non-small cell lung cancer line (GLC-82). Trypan
blue staining for assessing vital cell number to be seed and
MTT assay was used as cell proliferation test. Lentivus for HDAC2 was used to silence its mRNA. Western blotting analysis was used for protein extracts, and
ELISA was done on culture media for cytokines (IL-6, IL-8 and TNF-alpha) release.
Hydrogen peroxide (H2O2) was used to induce oxidative
stress. Our results have shown that Lentivirus containing the
shHDAC2 in GLC-82 cells was able to reduce protein expression of HDAC2.
In the GLCshHDAC2 cell line obtained, H2O2 induced a
significant increase in cytokines release and ERK1/2 phosphorylation (P 0.01);
a significant decrease of RECK activation (P 0.01);
a significant increased activation (P 0.01)
of both MMP-2 and MMP-9 and an increased activation of NF-κB, MyD88, TRAF-6, TRADD, TRAF-2. In GLCshHDAC2 cell, the treatment
with simvastatin (30 μM), significantly affected all the biochemical markers
examinated (P 0.01). In conclusion, from our
report emerge, that simvastatin is able per
se to inhibit oxidative stress in lung cancer cells, overcoming HDAC2
expression.