Antiproliferative activity of contragestazol (DL111-IT) in murine and human tumor models in vitro and in vivo
Antiproliferative activity of contragestazol (DL111-IT) in murine and human tumor models in vitro and in vivo
复制标题
DOI：
10.1007/s00280-005-0049-9
复制
发表时间：
2005
影响因子：
3
通讯作者：
Bo Yang;Qiao‐jun He;Danyan Zhu;Y. Lou;R. Fang
中科院分区：
文献类型：
--
作者：
Bo Yang;Qiao‐jun He;Danyan Zhu;Y. Lou;R. Fang
目的：评价反式地塞米松(DL111-IT)的体内外抗增殖活性，并探讨其可能的分子机制。方法：采用四甲基偶氮唑蓝/台盼蓝拒染法检测DL111-IT对小鼠和人肿瘤模型的杀伤能力，流式细胞仪检测细胞周期；结果：DL111-IT对12种肿瘤细胞生长抑制作用较强，IC50值为4.1~19.7μg/ml，DL111-IT 12.5~50.0 mg/kg连续给药9d对肉瘤S180和H22荷瘤小鼠的抑制率分别为55.9%和55.6%。人卵巢癌(HO-8910)移植瘤研究表明，DL111-IT(12.5~50.0 mg/kg)9次给药(15d内)对肿瘤生长有明显抑制作用，抑制率为17.0~64.3%。DL111-IT诱导HO-8910细胞G1期停滞，pRb、CDK4和Cyclin D1过表达，提示细胞周期调控可能参与了DL111-IT的抗癌作用。结论：DL111-IT通过细胞周期调节途径抑制肿瘤细胞的体外和体内增殖。
Purposes: To evaluate the antiproliferative activity of contragestazol (DL111-IT) in vitro and in vivo and to elucidate potential molecular mechanisms.Methods: Cell killing ability of DL111-IT was measured by MTT/Trypan blue exclusion method and murine and human tumor models; cell cycle was analyzed by flow cytometry; pRb, CDK4 and Cyclin D1 expressions were detected by western blotting.Results: DL111-IT exhibited high efficiency on cell growth inhibition of 12 cancer cell lines, the IC50values were 4.1–19.7 μg/ml. In Sarcoma-180 (S180) and Hepatoma-22 (H22) tumor bearing mice models, the inhibition rates were 55.9 and 55.6%, respectively, at the doses of DL111-IT 12.5–50.0 mg/kg for 9 days consecutive administration. Human ovarian carcinoma (HO-8910) xenograft study showed that, nine administrations (within 15 days) of DL111-IT (12.5–50.0 mg/kg) significantly inhibited tumor growth with the inhibition rates ranging from 17.0 to 64.3%. DL111-IT induced G1 arrest and overexpression of pRb, CDK4 and Cyclin D1 were observed in HO-8910 cell line, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT.Conclusions: DL111-IT could inhibit the proliferation of cancer cells both in vitro and in vivo via a cell cycle regulation pathway.