新型维生素 D 羟基衍生物抑制黑色素瘤生长，并对正常黑素细胞显示出不同的影响。
Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes.
机构信息
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
出版信息
Anticancer Res. 2012 Sep;32(9):3733-42.
BACKGROUND/AIMS: To test the activity of novel hydroxyvitamin D(3) analogs (20(OH)D(3), 20,23(OH)(2)D and 1,20(OH)(2)D(3)) on normal and malignant melanocytes in comparison to 1,25(OH)(2)D(3).
MATERIALS AND METHODS
Human epidermal melanocytes and human and hamster melanoma cells were used to measure effects on proliferation and colony formation in monolayer and soft agar. Cell morphology and melanogenesis were also analyzed. QPCR was used to measure gene expression.
RESULTS
Novel secosteroids inhibited proliferation and colony formation by melanoma cells in a similar fashion to 1,25(OH)(2)D(3), having no effect on melanogenesis. These effects were accompanied by ligand-induced translocation of VDR to the nucleus. In normal melanocytes 1α-hydroxyderivatives (1,25(OH)(2)D(3) and 1,20(OH)(2)D(3)) had stronger anti-proliferative effects than 20(OH)D(3) and 20,23(OH)(2)D(3), and inhibited dendrite formation. The cells tested expressed genes encoding VDR and enzymes that activate or inactivate vitamin D(3).
CONCLUSION
Novel secosteroids show potent anti-melanoma activity in vitro with 20(OH)D(3) and 20,23(OH)(2)D(3) being excellent candidates for pre-clinical testing.
背景/目的：测试新型羟基维生素 D（3）类似物（20（OH）D（3）、20,23（OH）（2）D 和 1,20（OH）（2）D（3））与 1,25（OH）（2）D（3）相比在正常和恶性黑素细胞中的活性。
材料和方法
用人表皮黑素细胞和人及仓鼠黑素瘤细胞测量单层和软琼脂中增殖和集落形成的影响。还分析了细胞形态和黑素生成。使用 QPCR 测量基因表达。
结果
新型甾体抑制黑素瘤细胞的增殖和集落形成，其方式与 1,25（OH）（2）D（3）相似，对黑素生成没有影响。这些作用伴随着 VDR 配体诱导向核内易位。在正常黑素细胞中，1α-羟衍生物（1,25（OH）（2）D（3）和 1,20（OH）（2）D（3）比 20（OH）D（3）和 20,23（OH）（2）D（3）具有更强的抗增殖作用，并抑制树突形成。所测试的细胞表达编码 VDR 和激活或失活维生素 D（3）的酶的基因。
结论
新型甾体在体外具有很强的抗黑素瘤活性，20（OH）D（3）和 20,23（OH）（2）D（3）是临床前测试的优秀候选物。
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