Abstract B50: LDL receptor plays an important role in inhibition of prostate cancer cell proliferation by statin
Authors: Furuya Yosuke , Sekine Yoshitaka , Koike Hidekazu , Matsui Hiroshi , Suzuki Kazuhiro 
Published: May 2013

Abstract
Object: Statins have been studied for their proapoptic and antimetastatic effects, which may make them relevant to cancer prevention or treatment. Some studies have shown a decreased risk of developing cancer in general. Concerning prostate cancer, the anticancer effect of statins is controversial. In vitro, some reports showed that statins have biological activities which inhibit PC proliferation, lowering the raft cholesterol content and inhibition of cyclin-dependent-kinase- 2 activity. However, the exact mechanisms of their anticancer action are still unclear.
Statins lower cholesterol by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway of cholesterol synthesis. In normal cells, a decrease of intracellular cholesterol level induces an expression of low-density lipoprotein receptor (LDLR). On the other hand, it is reported that the regulation of LDLR expression is lacking in androgen-independent prostate cancer. We assessed the effect of several statins on the proliferation of prostate cancer cells, and studied the relationship between the expression of LDLR and the effect of statins.
Methods: Simvastain, lovastatin, NK104, fluvastatin, pravastatin were used for our experiments. We examined the effect of statins on LNCaP and PC-3 cell proliferations by MTS assay, and evaluated the expression of LDLR after administrations of statins by Western blotting. Intracellular cholesterol levels of LNCaP and PC-3 cells were measured after administration of simvastatin. Furthermore, small interfering RNA (siRNA) were used to knock down the gene expression of LDLR.
Results: In both prostate cancer cell lines, lipophilic statins inhibited cell proliferations. But pravastatin, water-soluble statin, did not significantly inhibit cell proliferations. In PC-3 cells, low dose statins (1 μM) inhibited cell proliferation. Otherwise, in LNCaP cells, only high dose statins (100 μM) inhibited cell proliferation. In LNCaP cells, the protein expression of LDLR was increased after treatment of statins. On the other hand, In PC-3 cells, statin did not regulate the expression of LDLR. In PC-3 cells, intracellular cholesterol levels were significantly decreased by simvastatin, but not in LNCaP cells. After knocking down of LDLR expression by LDLR siRNA, cell proliferation was inhibited by 10 μM of simvastatin in LNCaP cells.
Conclusion: Statins inhibited proliferation of PC-3 cells and LNCaP cells after transfection of LDLR siRNA. These findings suggested that LDLR plays an important role in inhibition of prostate cancer cell proliferation by statin, and statins could be more effective in androgen-independent prostate cancer which lacks an ability to regulate an expression of LDLR. Future studies on the effect of diet and lipid-modulating drugs may uncover new approaches for the prevention and treatment of prostate cancer.
Citation Format: Yosuke Furuya, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Kazuhiro Suzuki. LDL receptor plays an important role in inhibition of prostate cancer cell proliferation by statin [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B50.