Kawa S, Nikaido T, Aoki Y, Zhai Y, Kumagai T, Furihata K, Fujii S, Kiyosawa K
The Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Br J Cancer. 1997;76(7):884-9. doi: 10.1038/bjc.1997.479.
To obtain information regarding the growth-inhibitory effect of 1,25-dihydroxyvitamin D3 and its non-calcaemic analogue 22-oxa-1,25-dihydroxyvitamin D3 on pancreatic cancer cell lines, differences in the effects of G1-phase cell cycle-regulating factors were studied in vitamin D-responsive and non-responsive cell lines. Levels of expression of cyclins (D1, E and A), cyclin-dependent kinases (2 and 4) and cyclin-dependent kinase inhibitors (p21 and p27) were analysed by Western blotting after treatment with these compounds. In the responsive cells (BxPC-3, Hs 700T and SUP-1), our observations were: (1) marked up-regulation of p21 and p27 after 24 h treatment with 10(-7) mol l(-1) 1,25-dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3; and (2) marked down-regulation of cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors after 7 days' treatment. In non-responsive cells (Hs 766T and Capan-1), no such changes were observed. In conclusion, vitamin D analogues up-regulate p21 and p27 as an early event, which in turn could block the G1/S transition and induce growth inhibition in responsive cells.
为获取有关1,25 - 二羟基维生素D3及其非钙调类似物22 - 氧杂 - 1,25 - 二羟基维生素D3对胰腺癌细胞系生长抑制作用的信息，我们研究了维生素D反应性和非反应性细胞系中G1期细胞周期调节因子作用的差异。在用这些化合物处理后，通过蛋白质免疫印迹法分析细胞周期蛋白（D1、E和A）、细胞周期蛋白依赖性激酶（2和4）以及细胞周期蛋白依赖性激酶抑制剂（p21和p27）的表达水平。在反应性细胞（BxPC - 3、Hs 700T和SUP - 1）中，我们的观察结果如下：（1）用10^(-7) mol l^(-1)的1,25 - 二羟基维生素D3和22 - 氧杂 - 1,25 - 二羟基维生素D3处理24小时后，p21和p27显著上调；（2）处理7天后，细胞周期蛋白、细胞周期蛋白依赖性激酶和细胞周期蛋白依赖性激酶抑制剂显著下调。在非反应性细胞（Hs 766T和Capan - 1）中，未观察到此类变化。总之，维生素D类似物作为早期事件上调p21和p27，这反过来可能会阻断G1/S期转换并诱导反应性细胞的生长抑制。
