Iα,25-dihydroxyvitamin D3 (calcitriol) and its analogue, 19-nor-Iα,25(OH)2D2, potentiate the effects of ionising radiation on human prostate cancer cells
Iα,25-dihydroxyvitamin D3 (calcitriol) and its analogue, 19-nor-Iα,25(OH)2D2, potentiate the effects of ionising radiation on human prostate cancer cells
复制标题
DOI：
10.1038/sj.bjc.6601161
复制
发表时间：
2003-08-18
影响因子：
8.8
通讯作者：
Koumenis, C
中科院分区：
文献类型：
--
作者：
Dunlap, N;Schwartz, GG;Koumenis, C
体外放射治疗或近距离放射治疗是前列腺癌的既定治疗方式。大约30%的局限性前列腺癌患者在照射部位复发。电离辐射（IR）的继发性影响，例如肠道和膀胱并发症，是常见的。因此，寻找生物反应调节剂，可以加强辐射的治疗效果和限制严重副作用的发生是前列腺癌治疗中的一项重要任务。1 α，25-二羟基维生素D-3（骨化三醇），维生素D的活性代谢物，及其类似物正在研究用于治疗几种恶性肿瘤，包括前列腺癌。在这里，我们报告了1 α，25-二羟维生素D-3及其低钙类似物19-去甲-1 α，25-（OH）（2）D-2（Zemplar（R））与IR协同作用，抑制体外人前列腺癌细胞的生长。1 α，25-二羟维生素D-3增强IR诱导的LNCaP细胞凋亡，纳摩尔剂量的1 α，25-二羟维生素D-3和19-去甲-1 α，25-（OH）（2）D-2在放射生物学相关剂量的IR（1 - 2戈伊）下显示出对LNCaP细胞生长的协同抑制作用。在较高剂量的IR下，1 α，25-二羟维生素D-3和IR或19-去甲-1 α，25-（OH）（2）D-2和IR的组合产生中度拮抗作用。放射生物学相关剂量的放射协同效应表明，1 α，25-二羟基维生素D-3或19-去甲-1 α，25-（OH）（2）D-2与IR联合使用可减少临床给予的放射剂量，从而可能降低治疗相关的发病率。
Radiotherapy with external beam radiation or brachytherapy is an established therapeutic modality for prostate cancer. Approximately 30% of patients with localised prostate cancer relapse at the irradiated site. Secondary effects of ionising radiation (IR), for example, bowel and bladder complications, are common. Thus, the search for biological response modifiers that could potentiate the therapeutic effects of radiation and limit the occurrence of serious side effects is an important task in prostate cancer therapy. 1alpha,25-Dihydroxyvitamin D-3 (calcitriol), the active metabolite of vitamin D, and its analogues are under investigation for the treatment of several malignancies including prostate cancer. Here, we report that 1alpha,25-dihydroxyvitamin D-3 and its less calcaemic analogue 19-nor-1alpha,25-(OH)(2)D-2 (Zemplar(R)) act synergistically with IR to inhibit the growth of the human prostate cancer cells in vitro. 1alpha,25-dihydroxyvitamin D-3 potentiated IR-induced apoptosis of LNCaP cells, and nanomolar doses of 1alpha,25-dihydroxyvitamin D-3 and 19-nor-1alpha,25-(OH)(2)D-2 showed synergistic inhibition of growth of LNCaP cells at radiobiologically relevant doses of IR (1 - 2 Gy). At higher doses of IR, the combination of 1alpha,25-dihydroxyvitamin D-3 and IR or 19-nor-1alpha,25-(OH)(2)D-2 and IR resulted in moderate antagonism. The synergistic effect at radiobiologically relevant doses of radiation suggests that a combination of 1alpha,25-dihydroxyvitamin D-3 or 19-nor-1alpha,25-(OH)(2)D-2 with IR could permit a reduction in the dose of radiation given clinically and thus potentially reduce treatment-related morbidity.