Cross H S, Huber C, Peterlik M
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Biochem Biophys Res Commun. 1991 Aug 30;179(1):57-62. doi: 10.1016/0006-291x(91)91333-8.
Depending on culture in either "low Ca++" (0.25 mM) or "normal Ca++" (1.8 mM) medium, human colon adenocarcinoma-derived CaCo-2 cells exhibit differential sensitivity to the antiproliferative action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and of two side-chain modified analogs, 1,25S,26-trihydroxy-delta 22-vitamin D3 (Ro 23-4319) and 1,25-dihydroxy-delta 16-23yne-vitamin D3 (Ro 23-7553). CaCo-2 cells cultured under low Ca++ conditions exhibit a high proliferative potential, and in these cells, all vitamin D compounds under investigation significantly inhibit [3H]thymidine incorporation into cellular DNA at greater than or equal to 10(-10) M. The rank order of biopotency is: Ro 23-7553 greater than or equal to Ro 23-4319 greater than 1,25(OH)2D3. At 1.8 mM Ca++, only Ro 23-7553 is able to inhibit proliferation of CaCo-2 cells. Parallel to their antiproliferative action, all three vitamin D compounds stimulate akaline phosphatase activity in CaCo-2 cells, indicating their ability to induce differentiated functions at the same time as they reduce neoplastic cell growth.
根据在“低钙++”（0.25 mM）或“正常钙++”（1.8 mM）培养基中的培养情况，源自人结肠腺癌的CaCo-2细胞对1,25-二羟基维生素D3（1,25(OH)2D3）以及两种侧链修饰类似物1,25S,26-三羟基-δ22-维生素D3（Ro 23-4319）和1,25-二羟基-δ16-23炔-维生素D3（Ro 23-7553）的抗增殖作用表现出不同的敏感性。在低钙++条件下培养的CaCo-2细胞具有较高的增殖潜能，在这些细胞中，所有研究的维生素D化合物在大于或等于10(-10) M时均能显著抑制[3H]胸苷掺入细胞DNA。生物活性的顺序为：Ro 23-7553≥Ro 23-4319＞1,25(OH)2D3。在1.8 mM钙++时，只有Ro 23-7553能够抑制CaCo-2细胞的增殖。与它们的抗增殖作用平行，所有三种维生素D化合物均能刺激CaCo-2细胞中的碱性磷酸酶活性，表明它们在减少肿瘤细胞生长的同时能够诱导分化功能。
