1α,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2

被引:28
作者
Akhter, J [1 ]
Lu, Y [1 ]
Finlay, I [1 ]
Pourgholami, MH [1 ]
Morris, DL [1 ]
机构
[1] Univ New S Wales, St George Hosp, Dept Surg, Sydney, NSW 2217, Australia
来源
AUSTRALIAN AND NEW ZEALAND JOURNAL OF SURGERY | 2001年 / 71卷 / 07期
关键词
growth inhibitors; hepatocellular carcinoma; HepG2; proliferation; vitamin D-3;
D O I
10.1046/j.1440-1622.2001.02147.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: 1 alpha ,25-dihydroxyvitamin D-3 (1,25[OH](2)D-3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. Methods: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)(2)D-3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [H-3]thymidine, and cell numbers were determined by trypan blue exclusion counting. Results: 1,25(OH)(2)D-3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10(-10) mol/L after 5 days of treatment with 1,25(OH)(2)D-3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)(2)D-3 (10(-10) and 10(-11) mol/L) when 1,25(OH)(2)D-3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)(2)D-3. When HepG2 cells were treated with 10(-8) mol/L 1,25(OH)(2)D-3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. Conclusions: 1,25(OH)(2)D-3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D-3.
引用
收藏
页码:414 / 417
页数:4
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