Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins.
Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins.
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DOI：
10.1016/j.prnil.2016.02.003
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发表时间：
2016-06
影响因子：
3
通讯作者：
Suzuki K
中科院分区：
文献类型：
--
作者：
Furuya Y;Sekine Y;Kato H;Miyazawa Y;Koike H;Suzuki K
目前关于他汀类药物的抗肿瘤作用已有一些报道。他汀类药物通过抑制3-羟基-3-甲基戊二酰辅酶A还原酶来降低血液中的胆固醇水平。这种酶的抑制降低细胞内胆固醇的合成。因此，低密度脂蛋白受体（LDLr）的表达增加，从血液中输入更多的胆固醇。在这项研究中，我们评估了他汀类药物对前列腺癌细胞增殖的影响，并研究了LDLr的表达与他汀类药物的作用之间的关系。实验中使用辛伐他汀。我们研究了辛伐他汀对PC-3和LNCaP细胞增殖的影响，使用MTS试验，并评估了LDLr的表达后，辛伐他汀管理的定量聚合酶链反应和蛋白质印迹。在给予辛伐他汀后测定前列腺癌细胞中细胞内胆固醇水平。此外，使用小干扰RNA（siRNA）来敲低LDLr的基因表达。在PC-3细胞中，辛伐他汀抑制细胞增殖。在LNCaP细胞中，只有高浓度的辛伐他汀（100μM）才能抑制细胞增殖。在LNCaP细胞中，辛伐他汀增加LDLr的蛋白水平。在PC-3细胞中，LDLr的蛋白水平不受调节。在PC-3细胞，但不是在LNCaP细胞，细胞内胆固醇水平显着降低辛伐他汀。在LNCaP细胞中，通过siRNA敲低LDLr表达后，细胞内胆固醇水平降低，并且细胞增殖被辛伐他汀抑制。辛伐他汀通过降低细胞胆固醇抑制前列腺癌细胞生长，并且在雄激素非依赖性前列腺癌中可能更有效，其中存在LDLr表达调控的丧失。LDLr在他汀类药物诱导的前列腺癌细胞增殖抑制中发挥重要作用。这些结果表明，未来的研究评估他汀类药物的降胆固醇作用可能会导致新的方法来预防和治疗前列腺癌。
There are some reports about the antitumor effects of statins in these days. Statins decrease the level of cholesterol in the blood by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Inhibition of this enzyme decreases intracellular cholesterol synthesis. Thus, the expression of low-density lipoprotein receptor (LDLr) is increased to import more cholesterol from the bloodstream. In this study, we assessed the effects of statins on the proliferation of prostate cancer cells, and studied the relationship between the expression of LDLr and the effects of statins. Simvastatin was used in the experiments. We studied the effect of simvastatin on PC-3 and LNCaP cell proliferation using the MTS assay, and evaluated the expression of LDLr after administration of simvastatin by quantitative polymerase chain reaction and Western blotting. Intracellular cholesterol levels in the prostate cancer cells were measured after administration of simvastatin. Furthermore, small interfering RNA (siRNA) was used to knockdown the gene expression of LDLr. In PC-3 cells, simvastatin inhibited cell proliferation. In LNCaP cells, only a high concentration of simvastatin (100μM) inhibited cell proliferation. In LNCaP cells, the protein level of LDLr was increased by simvastatin. In PC-3 cells, the protein levels of LDLr were unregulated. In PC-3 cells, but not in LNCaP cells, intracellular cholesterol levels were significantly decreased by simvastatin. After knocking down LDLr expression by siRNA, intracellular cholesterol levels were decreased, and cell proliferation was inhibited by simvastatin in LNCaP cells. Simvastatin inhibited prostate cancer cell growth by decreasing cellular cholesterol and could be more effective in androgen-independent prostate cancer, where there is loss of regulation of LDLr expression. LDLr was shown to play an important role in the statin-induced inhibition of prostate cancer cell proliferation. These results suggest that future studies evaluating the cholesterol-lowering effects of statin may lead to new approaches to the prevention and treatment of prostate cancer.