Simvastatin Therapy for Drug Repositioning to Reduce the Risk of Prostate Cancer Mortality in Patients With Hyperlipidemia

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD). A total of 15,264 PCa patients with hyperlipidemia records and medical claims from the Registry of Catastrophic Illness were enrolled. The patients were divided into two cohorts based on their statin use before the diagnosis of PCa: statin users (n = 1,827) and non-statin users (n = 1,826). The results showed that patients who used statins exhibited a significantly reduced risk of mortality from PCa [adjusted hazard ratio (HR) = 0.84, 95% CI = 0.73–0.97]. Analysis of the cumulative defined daily dose (DDD) indicated that patients who were prescribed simvastatin ≥ 180 DDD had a dramatically decreased risk of death from PCa (adjusted HR = 0.63; 95% CI = 0.51–0.77). This population-based cohort study demonstrated that statin use significantly decreased the mortality of PCa patients, and that this risk was inversely associated with the cumulative DDD of simvastatin therapy. The results of this study revealed that statins may be used for drug repositioning and in the development of a feasible approach to prevent death from PCa.

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

“…Among these drugs, statins are widely used to retard the atherosclerosis in patients with hyperlipidemia (Macan et al, 2015). In fact, these drugs have also been reported to present anti-inflammatory, anticancer, antioxidant and immunomodulatory effects (Chen et al, 2018;Rizvi et al, 2019). Experiments in vivo and in vitro have shown that statins protect organism damage from oxidative stress by eliminating superoxide anion and hydroxyl radicals (Murakami et al, 2018).…”

Simvastatin Sensitizes Radioresistant Prostate Cancer Cells by Compromising DNA Double-Strand Break Repair

“…Clinical studies have shown that statins decrease the incidence of advanced PCa, including radioresistant PCa ( Hindler et al, 2006 ; Pisanti et al, 2014 ). In addition, our recent studies using a population-based cohort demonstrated that statin prescriptions remarkably reduced the risk of death in PCa patients undergoing radiotherapy ( Sun et al, 2015 ; Chen et al, 2018 ). Although the radiosensitizing properties of statins and their potential effects in inhibiting PCa have been reported, the molecular mechanism underlying this outcome has not been clearly explored ( Alfaqih et al, 2017 ).…”

Selected pharmacotherapy agents as antiproliferative and anti‐inflammatory compounds

“…Repurposed medications can likewise minimize a great percentage of the early expense and time expected to offer a medication for sale to the public, thereby cutting the time between the research bench work and treatment at bedside (Papapetropoulos & Szabo, ). Simvastatin treatment experienced medication repositioning to diminish the danger of prostate malignant growth mortality in patients with hyperlipidemia (Chen et al, ). Colesevelam as a monotherapy of essential hyperlipidemia could be endorsed to improve diabetes control (Fonseca, Rosenstock, Wang, Truitt, & Jones, ; Sekhri & Saha, ).…”