Simvastatin Action Is Not Related to HDAC2 Expression in Non-Small Cell Lung Cancer (NSCLC)

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). T rypan blue staining for assessing vital cell number to be s e ed 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 (H 2 O 2 ) was used to induce oxidative stress. Our results have show n that Lentivirus containing the shHDAC2 in GLC-82 cells was able to reduce protein expression of HDAC2. In the GLCshHDAC2 cell line obtained, H 2 O 2 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- κ B, 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.