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

Journal of Cancer Therapy 2016年第12期7卷 939-952页

作者： Gallelli Luca Falcone Daniela Perri Mariarita Erika Cione pelaia girolamo Mesuraca Maria Terracciano Rosa Spaziano Giuseppe D’Agostino Bruno Navarra Michele Savino Rocco Department of Health Science University of Catanzaro Catanzaro Italy Department of Pharmacy Health and Nutritional Science University of Calabria Cosenza Italy Department of Medical and Surgical Sciences University of Catanzaro Catanzaro Italy Department of Experimental Medicine School of Medicine Second University of Naples Naples Italy Department of Drug Sciences and Health Products University of Messina Messina Italy

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.

关键词： Lung Adenocarcinoma Cells HDAC2 Statins Cell Proliferation Cytokines

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