Statin Use and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies

Bansal, Dipika; Undela, Krishna; D’Cruz, Sanjay; Schifano, Fabrizio

doi:10.1371/journal.pone.0046691

Cited by 184 publications

(179 citation statements)

References 53 publications

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…Previous studies have shown that statins can prolong survival, while others have reported no benefits in cancer patients (1). Concerning prostate cancer, the anticancer effect of statins is controversial (2,3). We previously reported that statins inhibit prostate cancer progression via suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and increasing ANXA10 (4,5).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC‑3 cells via an AKR1C3 mechanism

et al. 2017

View full text Add to dashboard Cite

Abstract.Statins have become of interest in research due to their anticancer effects. However, the exact mechanism of their anticancer properties remains unclear. The authors previously reported that statins decrease intracellular cholesterol levels in androgen-independent prostate cancer cells. In de novo androgen synthesis, cholesterol is the primary material and certain enzymes have important roles. The present study aimed to determine whether simvastatin alters the expression of androgen synthesis-associated enzymes in androgen-independent prostate cancer cells. A novel combination therapy of statins and other drugs that inhibit the overexpression of enzymes involved in androgen synthesis was explored. The cytotoxicity of simvastatin and meclofenamic acid was assessed in prostate cancer cells using MTS and migration assays. Testosterone and dihydrotestosterone concentrations in the culture medium were measured using liquid chromatography-tandem mass spectrometry. RAC-α-serine/threonine-protein kinase (Akt) phosphorylation was detected by western blot analysis. Following treatment with simvastatin, aldo-keto reductase family 1 member C3 (AKR1C3) expression increased in PC-3 (>60-fold) and LNCaP-LA cells, however not in 22Rv1 cells. Small interfering (si)RNA was used to clarify the effects of AKR1C3 expression. The reduction in AKR1C3 expression in PC-3 cells following siRNA transfection was not associated with basal cell proliferation and migration; however, treatment with simvastatin decreased cell proliferation and migration. The combination of simvastatin and meclofenamic acid, an AKR1C3 inhibitor, further enhanced the inhibition of cell proliferation and migration compared with treatment with either drug alone. Furthermore, treatment with simvastatin attenuated insulin-like growth factor 1-induced Akt activation; however, the combination of simvastatin and meclofenamic acid further inhibited Akt activation. These results suggest that the combination of simvastatin and meclofenamic acid may be an effective strategy for the treatment of castration-resistant prostate cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC‑3 cells via an AKR1C3 mechanism

et al. 2017

View full text Add to dashboard Cite

show abstract

“…12) Epidemiological studies have shown a reduced risk of advanced prostate cancer with the use of statins. [13][14][15][16] Statin use was also found to be associated with a reduction in the risk of biochemical recurrence in patients with prostate cancer 17) and a decreased risk of cancer mortality. 18) Recent studies have shown statin drugs including atorvastatin (Lipitor ® ) inhibit proliferation and induce apoptosis of prostate cancer cells.…”

mentioning

confidence: 98%

Mechanistic Study of Inhibitory Effects of Metformin and Atorvastatin in Combination on Prostate Cancer Cells <i>in Vitro</i> and <i>in Vivo</i>

Wang

Huang

Zhang

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres. Metformin and atorvastatin in combination had a potent inhibitory effect on nuclear factor-kappaB (NF-κB) activity and caused strong decreases in the expression of its downstream anti-apoptotic gene Survivin. Moreover, strong decreases in the levels of phospho-Akt and phosphorextracellular signal-regulated kinase (Erk)1/2 were found in the cells treated with the combination. The in vivo study showed that treatment of severe combined immunodeficient (SCID) mice with metformin or atorvastatin alone resulted in moderate inhibition of tumor growth while the combination strongly inhibited the growth of the tumors. Results of the present study indicate the combination of metformin and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.Key words prostate cancer; atorvastatin; metformin; apoptosis; combination Prostate cancer is one of the common types of malignant disease in males in the world and is the second leading cause of cancer-related death in the United States. The American Cancer Society estimates for 2016 approximately 180890 new cases will be diagnosed and 26120 men will die of the disease, accounting for about 8.3% of male cancer-related deaths. 1)Androgen deprivation therapy is an effective treatment for advanced prostate cancer. Unfortunately, almost all patients treated with androgen deprivation therapy will progress to castration-resistant prostate cancer (CRPC).2,3) Docetaxel is the most commonly prescribed first-line chemotherapy for CRPC. 4) Although docetaxel provides a modest (2.4-month) increase in median overall survival, many patients with CRPC cannot tolerate this cytotoxic chemotherapy due to advanced age, medical comorbidities, or limited bone marrow reserves. 5)Therefore, the identification of an effective alternative therapy with less toxicity may lead to increased survival and an improved QOL.Metformin is a well-established agent for the treatment of type II diabetes. In addition to its efficacy in lowering glucose levels, recent reports indicate it may have antitumor effects in various cancers, including prostate cancer. 6) Diabetic patients receiving metformin have been shown to have a reduced cancer incidence and a decrease in cancer-specific mortality.7) Further, epidemiologic evidence revealed a decreased incidence of prostate cancer in men taking metformin, 8,9) and both animal and in vitro models demonstrate its activity in prostate cancer cell lines. 10,11) Finall...

show abstract

“…In addition, statins exert proapoptotic, antiangiogenic, and immunomodulatory effects, which may prevent cancer growth [1,2] . Indeed, several observational studies and meta-analyses have shown that statin use may be associated with reduced risk of prostate cancer [3] , hepatocellular cancer [4] , gastric cancer [5] and esophageal cancer [6] but not others [7,8] . More recently, there has been greater interest in the potential role of statins in modifying cancer outcomes and mortality.…”

Section: Statins and Cancer Mortalitymentioning

confidence: 99%

Statin a day keeps cancer at bay

Singh¹

2013

WJCO

View full text Add to dashboard Cite

In addition to cholesterol reduction, statins, currently the most commonly prescribed drug in the world, have been shown to have anti-neoplastic and immunomodulatory effects. Several observational studies and meta-analyses have shown reduction in risk of multiple cancers. More recently there has been an increasing interest in the potential role of statins as adjuvant therapy after cancer diagnosis and in modifying cancer mortality. Although post-hoc analyses of randomized controlled trials of statins for cardiovascular outcomes have not shown reduction in the risk of cancer mortality with statin use, these studies lack sufficient power to detect a significant difference in cancer outcomes. Recently, in a Danish nationwide population-based cohort study, Nielsen et al showed a 15% reduction in all-cause and cancer-specific mortality in statin users as compared to non-users. Improved survival with statin exposure was seen in 13/27 cancer subtypes, including the 4 most common cancers -lung, prostate, colorectal and breast. In this commentary, we examine this important study, review its implications and limitations, and briefly discuss impact of other drugs like metformin and aspirin that also exhibit anti-neoplastic effects. Key words: Statins; Cancer; Mortality; Chemoprevention; Metformin Core tip: With increasing economic burden of cancer care, cost-effective, preventive strategies are in focus. Commonly used drugs like statins, metformin and aspirin have been shown to have anti-neoplastic effects and are attractive candidates for cancer chemoprevention and reducing cancer-related mortality. Recently, in a Danish nationwide population-based cohort study, statin users had 15% reduction in all-cause and cancer-specific mortality as compared to non-users. These results are encouraging and show that statin use may be associated with reduced cancer mortality across different subgroups and cancer sites. However, several confounding variables remain, which merit further evaluation before this can change clinical practice.Singh S, Singh PP. Statin a day keeps cancer at bay. World J

show abstract

Statin Use and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies

Cited by 184 publications

References 53 publications

Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC‑3 cells via an AKR1C3 mechanism

Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC‑3 cells via an AKR1C3 mechanism

Mechanistic Study of Inhibitory Effects of Metformin and Atorvastatin in Combination on Prostate Cancer Cells <i>in Vitro</i> and <i>in Vivo</i>

Statin a day keeps cancer at bay

Contact Info

Product

Resources

About