Effects of simvastatin on cell viability and proinflammatory pathways in lung adenocarcinoma cells exposed to hydrogen peroxide

BMC Clinical Pharmacology

Rocco Savino¹  Michele Navarra⁵  Rosario Maselli³  Giuseppe Spaziano²  Rosa Terracciano¹  Maria Mesuraca⁴  Bruno D’Agostino²  Girolamo Pelaia³  Monica Scaramuzzino¹  Daniela Falcone¹  Luca Gallelli¹ 

[1] Department of Health Science, University of Catanzaro, Catanzaro, Italy;Department of Experimental Medicine-Section of Pharmacology, School of Medicine, Second University of Naples, via Costantinopoli 16, 80136 Naples, Italy;Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy;Department of Experimental Medicine, University of Catanzaro, Catanzaro, Italy;Department of Drug Sciences and Health Products, University of Messina, IRCCS centro neurolesi “Bonino-Pulejo”, Messina, Italy

关键词: Simvastatin;    IL-8;    Innate immunity;    Matrix metalloproteinases;    NF-κB;    Lung cancer;   

Others  :  1084547
DOI  :  10.1186/2050-6511-15-67

 received in 2014-04-19, accepted in 2014-11-18,  发布年份 2014

【 摘 要 】

Lung cancer is characterized by a high mortality rate probably attributable to early metastasis. Oxidative stress is involved in development and progression of lung cancer, through cellular and molecular mechanisms which at least in part overlap with proinflammatory pathways. Simvastatin is a statin with pleiotropic effects that can also act as an anti-oxidant agent, and these pharmacologic properties may contribute to its potential anti-cancer activity. Therefore, the aim of this study was to evaluate, in the human lung adenocarcinoma cell line GLC-82, the effects of a 24-hour treatment with simvastatin on hydrogen peroxide (H₂O₂)-induced changes in cell viability, ERK phosphorylation, matrix metalloproteinase (MMP) expression, innate immunity signaling, NF-κB activation and IL-8 secretion. Cell counting was performed after trypan blue staining, cell proliferation was assessed using MTT assay, and apoptosis was evaluated through caspase-3 activation and Tunel assay. Western blotting was used to analyze protein extracts, and IL-8 release into cell culture supernatants was assessed by ELISA. Our results show that simvastatin (30 μM) significantly (P <0.01) inhibited the proliferative effect of H₂O₂ (0.5 mM) and its stimulatory actions on ERK1/2 phosphorylation, NF-κB activation and IL-8 production. Furthermore, simvastatin decreased H₂O₂-mediated induction of the cellular expression of MMP-2 and MMP-9, as well as of several components of the signaling complex activated by innate immune responses, including MyD88, TRAF2, TRAF6 and TRADD. In conclusion, these findings suggest that simvastatin could play a role in prevention and treatment of lung cancer via modulation of important proinflammatory and tumorigenic events promoted by oxidative stress.

【 授权许可】

   
2014 Gallelli et al.; licensee BioMed Central Ltd.

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