Akhter J, Chen X, Bowrey P, Bolton E J, Morris D L
University of New South Wales, Department of Surgery, Sydney, Australia.
Dis Colon Rectum. 1997 Mar;40(3):317-21. doi: 10.1007/BF02050422.
In this study, we investigated the effect of the vitamin D3 analog, EB1089, on the growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model.
BALB/c Nu/Nu nude mice were inoculated subcutaneously with 10(6) LoVo cells. EB1089 dissolved in isopropanol was administered intraperitoneally and orally on alternate days at doses of 0.1, 0.5, and 2.5 microg/kg/day. Control animals received isopropanol alone. Tumor volumes estimated using the formula 0.5 X length X (width)2. The tumor kinetic index was determined by immunohistochemical detection of proliferating cell nuclear antigen.
Significant dose-dependent inhibition of tumor growth was seen. After 20 days of treatment with 0.1 microg/kg/day EB1089, mean tumor volume in treated mice was 41 to 49 percent less than that in control animals (P < 0.01). Significant inhibition of tumor growth was also seen with 0.5 microg/kg/day EB1089 after 22 days of treatment (51 percent of control P < 0.01). Treatment with 2.5 microg/kg/day resulted in weight loss that required termination of this group; these mice were subsequently found to be hypercalcemic. The tumor kinetic index was significantly lower in tumors treated with 0.1 microg/kg/day EB1089 compared with that for control tumors (8 vs. 30 percent in controls).
These findings suggest that the vitamin D3 analog, EB1089, is a potent antiproliferative agent for some human colon cancers.
在本研究中，我们在裸鼠模型中研究了维生素D3类似物EB1089对人结肠癌细胞系LoVo皮下异种移植物生长的影响。
将10(6)个LoVo细胞皮下接种到BALB/c Nu/Nu裸鼠体内。将溶解于异丙醇的EB1089以0.1、0.5和2.5微克/千克/天的剂量隔日经腹腔和口服给药。对照动物仅接受异丙醇。使用公式0.5×长度×（宽度）2估算肿瘤体积。通过免疫组织化学检测增殖细胞核抗原确定肿瘤动力学指数。
观察到显著的剂量依赖性肿瘤生长抑制。用0.1微克/千克/天的EB1089治疗20天后，治疗组小鼠的平均肿瘤体积比对照组动物小41%至49%（P<0.01）。用0.5微克/千克/天的EB1089治疗22天后也观察到显著的肿瘤生长抑制（为对照组的51%，P<0.01）。用2.5微克/千克/天治疗导致体重减轻，该组需要终止实验；随后发现这些小鼠出现高钙血症。与对照肿瘤相比，用0.1微克/千克/天的EB1089治疗的肿瘤的肿瘤动力学指数显著更低（分别为8%和对照组的30%）。
这些发现表明，维生素D3类似物EB1089对某些人类结肠癌是一种有效的抗增殖剂。
