Co-targeting of HMG-Co-A Reductase and Cycloxygenase-2 for the Treatment of Non-small Cell Lung Cancer

Several studies have shown that high HMG-CO-A expression is associated with increased tumor progression and metastasis in clinical scenario. [...]inhibition of HMG-CO-A activity reduces the production of cholesterol and other isoprenoids which could affect their metabolic's and starve the tumors. Statins have been reported to exert anti-tumoral effects by modulating cell proliferation, apoptosis, angiogenesis and metastasis. [...]HMGCO-A expression may serve as a potential therapeutic target in cancer. Inhibition of Mevalonate pathway by HMG-Co-A reductase inhibitors could help in blocking the cell cycle check points, resulting in blocking of NSCLC proliferation. [...]upregulation of HMGCO-A in tumors improves inflammatory mediators such as cyclooxygenase-2 (COX-2) which is responsible for the angiogenesis, metastasis via thromboxane mediated PI3K/AKT activation.·· Blocking of COX-2 enzyme via COX-2 inhibitors such as celecoxib could be synergistic/ additive effect in combination with HMG-Co-A reductase inhibitors.