一种新型维生素D3类似物在体外对人角质形成细胞的生长抑制作用。

Growth inhibition of human keratinocytes by a new vitamin D3 analogue in vitro.

作者信息

Kobayashi T, Hashimoto K, Yoshikawa K

机构信息

Department of Dermatology, Osaka University School of Medicine, Japan.

出版信息

J Dermatol Sci. 1998 Jan;16(2):158-64. doi: 10.1016/s0923-1811(97)00045-5.

DOI:10.1016/s0923-1811(97)00045-5

PMID:9459129

Abstract

SM-10193 (26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3; F6-1,23(S),25-(OH)3D3) is one of the active vitamin D3 analogues, which is under exploration as a new therapeutic agent for psoriasis. In this paper, we present that SM-10193 induces the growth inhibition and differentiation of cultured normal human keratinocytes more effectively than 1,25(OH)2D3. The growth of keratinocytes was inhibited in the presence of 10(-11), 10(-10), 10(-9), 10(-8), 10(-7) and 10(-6) M of SM-10193 by 36.8, 42.1, 48.5, 47.6, 66.0 and 85.9% respectively. SM-10193 increased the number of involucrin positive cells (the marker for keratinocyte differentiation) from 4.9 +/- 0.1 to 12.5 +/- 0.8, 20.1 +/- 1.6 and 42.8 +/- 1.0% (P < 0.01) at 10(-8), 10(-7) and 10(-6) M, respectively. To elucidate the mechanism of SM-10193-induced growth inhibition, we analyzed cell cycle related distribution and the alteration of hyperphosphorylated and hypophosphorylated state of retinoblastoma protein (pRB). SM-10193 induces growth arrest in G1/G0 and G2 + M phases and an increase of the hypophosphorylated form of pRB more remarkably than 1,25(OH)2D3 does.

摘要

SM - 10193（26,26,26,27,27,27 - 六氟 - 1α,23(S),25 - 三羟基维生素D3；F6 - 1,23(S),25 - (OH)3D3）是活性维生素D3类似物之一，正作为银屑病的一种新型治疗药物进行研究。在本文中，我们指出SM - 10193比1,25(OH)2D3更有效地诱导培养的正常人角质形成细胞的生长抑制和分化。在10(-11)、10(-10)、10(-9)、10(-8)、10(-7)和10(-6) M的SM - 10193存在下，角质形成细胞的生长分别被抑制36.8%、42.1%、48.5%、47.6%、66.0%和85.9%。在10(-8)、10(-7)和10(-6) M时，SM - 10193使包壳蛋白阳性细胞（角质形成细胞分化的标志物）的数量分别从4.9±0.1增加到12.5±0.8、20.1±1.6和42.8±1.0%（P < 0.01）。为阐明SM - 10193诱导生长抑制的机制，我们分析了细胞周期相关分布以及视网膜母细胞瘤蛋白（pRB）的高磷酸化和低磷酸化状态的改变。SM - 10193比1,25(OH)2D3更显著地诱导细胞在G1/G0和G2 + M期停滞以及pRB低磷酸化形式的增加。