6,8-二-三氟甲基-7-乙酰基白杨素抗肝癌作用实验研究

目的:研究6,8-二-三氟甲基-7-乙酰基白杨素(dFMAChR)体内外抗肝癌作用。方法:MTT比色法测定dFMAChR对体外培养人肝癌细胞Hep G2细胞和人胚肝细胞L-02细胞增殖的影响;平皿克隆形成法及软琼脂克隆形成法测定dFMAChR对体外培养Hep G2细胞的锚定依赖性及非锚定依赖性生长作用;PI染色流式细胞术(FCM)分析dFMAChR对Hep G2细胞周期的影响;人肝癌裸鼠异种移植瘤模型治疗实验评价dFMAChR治疗人肝癌的有效性。结果:dFMAChR抑制体外培养人肝癌Hep G2细胞增殖和生长,其效价强度高于先导化合物白杨素(ChR),而对人胚肝(L-02)细胞的毒性小,其选择指数为42.96。PI染色FCM结果显示3.0μM,10.0μM,30.0μM的dFMAChR作用于Hep G2细胞48h后,其G1期累积细胞百分率分别为64.5%、69.1%、78.4%,较溶媒对照组和ChR 30.0μM的58.2%和68.3%有显著提高,呈现G1期阻滞现象。人肝癌裸鼠异种移植瘤模型治疗实验结果显示:dFMAChR对人肝癌异种移植瘤生长具有显著抑制作用,20,40,80 mg/kg的dFMAChR对移植瘤的瘤重抑制率分别为40.17%,47.41%和66.81%。结论:dFMAChR具有人肝癌治疗作用。

Experimental Study on Therapeutic Effect of Human Lever Carcinoma by 6,8 -ditrifluoromethy-7-acetoy Chrysin

Objective To study on the therapeutic effect of human lever carcinoma by 6,8-ditrifluoromethy-7-acetoy chrysin(dFMAChR) in vitro and vivo.Methods Human lever carcinoma(Hep G2) cells were cultured in vitro.The proliferative inhibition of dFMAChR on Hep G2 cells were examined by MTT assay.Clone-formation assay in plate and soft agar was used to test inhibition of clone formation of Hep G2 by dFMAChR.Flow cytometry(FCM) using PI staining was used to analyse the apoptosis and cell cycle change after treatment with dFMAChR.Human lever carcinoma xenograft in nude mouse model was established to investigate the anti-tumor effect of dFMAChR in vivo.Results dFMAChR inhibited proliferation and growth of Hep G2 cells in a dose-dependent manner,its efficacy was stronger than that of Chrysin.While there was no significant effect in L-02 cells.The selective index was 42.96.FCM analysis indicated that the rate of G1 phase cells was 64.5%,69.1%,78.4% respectively after treatment with various concentration 3.0,10.0,30.0μM of dFMAChR for 48h,which was higher than either the control group or the same concentration ChR-treated cells.The result revealed that dFMAChR can significantly arrest the cell cycle in G1 phase.Therapeutic trial of human lever carcinoma xenograft in nude mouse model indicated that dFMAChR significantly inhibited the growth of human lever carcinoma xenografts in Balb/c-nu mice.The tumor weight inhibitory rate of dFMAChR at 20,40,80 mg/kg was 40.17%,47.41%,66.81% respectively.Conclusion dFMAChR posseses human lever carcinoma therapeutical effect in vitro and in vivo.