Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of bcl-2
Calcitriol-induced apoptosis in LNCaP cells is blocked by overexpression of bcl-2
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DOI：
10.1210/en.141.1.10
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发表时间：
2000-01-01
期刊：
影响因子：
4.8
通讯作者：
Weigel, NL
中科院分区：
文献类型：
--
作者：
Blutt, SE;McDonnell, TJ;Weigel, NL
虽然维生素D在骨和矿物质代谢中的作用已被广泛研究，但维生素D受体在其他组织中的作用尚不清楚。1，25-二羟基维生素D（骨化三醇）可以作为正常组织中的分化剂，并可以抑制许多癌细胞系（包括LNCaP前列腺癌细胞）的生长。我们以前已经表明，骨化三醇导致LNCaP细胞在细胞周期的G（0）/G（1）期积累。在这项研究中，我们证明，骨化三醇也诱导LNCaP细胞凋亡。骨化三醇诱导的细胞凋亡伴随着Bcl-2和Bcl-X-L蛋白的下调，这两种蛋白都保护细胞免于经历凋亡。在凋亡控制中重要的其他蛋白质Bar、Mcl-1和Bcl-X-s不受骨化三醇处理的影响。我们发现Bcl-2的过表达阻断了骨化三醇诱导的细胞凋亡，并减少了但不能消除骨化三醇诱导的生长抑制。我们的结论是细胞周期和凋亡途径的调节参与骨化三醇在前列腺癌细胞中的作用。
While the role of vitamin D in bone and mineral metabolism has been investigated extensively, the role of the vitamin D receptor in other tissues is less well understood. 1,25-dihydroxyvitamin D, (calcitriol) can act as a differentiating agent in normal tissues and can inhibit the growth of many cancer cell lines including LNCaP prostate cancer cells. We have shown previously that calcitriol causes LNCaP cell accumulation in the G(0)/G(1) phase of the cell cycle. In this study, we demonstrate that calcitriol also induces apoptosis of LNCaP cells. The calcitriol-induced apoptosis is accompanied by a down-regulation of Bcl-2 and Bcl-X-L proteins, both of which protect cells from undergoing apoptosis. Other proteins important in apoptotic control, Bar, Mcl-1, and Bcl-X-s, are unaffected by calcitriol treatment. We find that overexpression of Bcl-2 blocks calcitriol-induced apoptosis and reduces, but does not eliminate, calcitriol-induced growth inhibition. We conclude that both regulation of cell cycle and the apoptotic pathway are involved in calcitriol action in prostate cancer cells.