Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells
Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells
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DOI：
10.1111/j.1442-2042.2006.01360.x
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发表时间：
2006-05-01
影响因子：
2.6
通讯作者：
Namiki, Mikio
中科院分区：
文献类型：
--
作者：
Asahi, Hideki;Mizokami, Atsushi;Namiki, Mikio
目的：双磷酸盐已被广泛用于治疗癌症引起的骨骼并发症。最近的研究表明，双磷酸盐可促进癌细胞以及骨转移部位破骨细胞的凋亡。为了确定双膦酸盐对前列腺癌的直接影响，我们检测了米诺膦酸盐对前列腺癌细胞生长以及凋亡相关蛋白和破骨细胞因子表达的影响。方法：PC-3。用氨基二膦酸米诺膦酸处理 DU145 和 LNCaP 细胞。然后评估bcl-2、bax、聚(ADP)-核糖聚合酶(PARP)、caspase-3、核因子κB配体受体激活剂(RANKL)、骨保护素(OPG)、基质金属蛋白酶-2(MMP-2)和甲状旁腺激素相关蛋白(PTHrP)的增殖、凋亡和表达。结果： 米诺膦酸钠抑制前列腺癌细胞的增殖。在米诺膦酸盐处理的 PC-3 细胞中观察到 DNA 片段化和 TUNEL 阳性细胞核。 Minodronate 降低 DU145 和 PC-3 细胞中的 bcl-2 表达并诱导 bax 表达、caspase-3 活性和 PARP 降解。米诺膦酸盐降低PC-3细胞中RANKL、PTHrP和MMP-2的表达。结论：我们的结果表明，二膦酸盐不仅直接促进细胞凋亡，而且降低前列腺癌细胞中促破骨细胞基因的表达。
Aim: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors.Methods: PC-3. DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappa B ligand (RANKL) osteoprotegerin (OPG), rnatrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed.Results: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells.Conclusions: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic,gene expression in prostate cancer cells.