Abstract
Background: Several epidemiological studies have reported decreased risk of advanced prostate cancer among men using statins, a widely used group of cholesterol-lowering drugs. The association is possibly linked to serum LDL reduction during statin therapy. We studied in vitro the importance of LDL on growth of normal and cancerous prostate epithelial cells and evaluated its association with growth reducing effect of simvastatin.
Methods: Four normal prostatic epithelial cell lines (P96E, P97E, PWR-1E, RWPE-1) and two cancer cell lines (LNCaP and VCaP) were grown in cholesterol-free conditions. Cells were treated with 1 µg/ml, 15 µg/ml or 50 µg/ml LDL, 100 nM or 10 µM simvastatin and/or 100 µM mevalonate for seven days. Cellular growth rate was measured with crystal violet staining.
Results: In normal epithelial cells, 1 µg/ml and 15 µg/ml LDL did not have marked effect on cell growth, while 50 µg/ml LDL had a growth reducing effect. Conversely, in cancer cells cellular growth was stimulated in direct correlation with LDL concentration. Simvastatin at 100 nM concentration caused clear growth reduction in normal epithelial cells, and 10 µM simvastatin had a cytotoxic effect. Growth reduction by 100 nM simvastatin was attenuated by increasing LDL concentrations, the effect being completely reversed by 15 µg/ml LDL. However, the cytotoxic effect of 10 µM simvastatin could not be reversed by LDL alone, but required combination of 100 µM mevalonate and 15 µg/ml LDL.
Conclusions: Our results demonstrate the importance of LDL for prostate cancer cell growth. The growth reducing effect of simvastatin depends on the level of extracellular LDL. Our study supports the epidemiological studies suggesting that statins’ prostate cancer risk reducing effects depend on LDL reduction. Hypercholesterolemia could be a prostate cancer risk factor.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A35.
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