The role of statins in lung cancer

Abstract

Lung cancer is one of the most common causes of cancer-related mortality in the 21^st century. Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase not only reduce the cholesterol levels in the blood and decrease the risk of cardiovascular disease but may also play an important role in the prevention and treatment of lung cancer. Statins have several antitumor properties including the ability to reduce cell proliferation and angiogenesis, decrease invasion and synergistic suppression of lung cancer progression. Statins induce tumor cell apoptosis by inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac, which are dependent on isoprenylation. Statins reduce angiogenesis in tumors by down-regulation of pro-angiogenic factors, such as vascular endothelial growth factor. In this review, the feasibility and efficacy of statins in the prevention and treatment of lung cancer are discussed.

Keywords: apoptosis; lung cancer; non-small cell lung cancer; statins.

Figure 1

Functional pathway and effect of HMG-CoA reductase enzyme on the activity of Rho/Ras

Figure 2

The most important effects of statins on lung cancer: inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, stopping the mevalonate production from HMG-CoA and reducing mevalonate level, inhibiting myocardial Rac1-GTPase activity in order to suppress the NADPH oxidase activity and ROS generation. Also statins are inhibitors of farnesyltransferase (FT) proteins, RAF/ERK and AKT pathways, inhibitors of the EGFR and anti-apoptotic protein Mcl-1 in animals and humans. Additionally, they have effects on cellular energy homeostasis by inducing LKB1 and AMPK activation, and by inducing p53 pathway and G1 cell cycle arrest, which prevents DNA damage