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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。
Objective: To study the anti-hepatoma effect of 6,8-bis-trifluoromethyl-7-acetylchrysin (dFMAChR) in vitro and in vivo. Methods: MTT assay was used to determine the effect of dFMAChR on the proliferation of Hep G2 cells and human embryonic hepatocytes L-02 cells cultured in vitro. The effects of dFMAChR on the growth of Hep G2 cells in vitro were determined by plate clone formation assay and soft agar colony formation assay The effect of dFMAChR on Hep G2 cell cycle was analyzed by PI staining flow cytometry (FCM). The therapeutic effect of dFMAChR on human hepatocellular carcinoma was evaluated by the treatment of human hepatocellular carcinoma xenograft model in nude mice. Results: dFMAChR inhibited the proliferation and growth of Hep G2 cells in vitro. The potency of dFMAChR was higher than that of lead chrysene (ChR) and less toxic to human embryonic liver (L-02) cells. The selection index was 42.96. PI-stained FCM results showed that the percentage of G1 phase cells in the G1 phase of dFMAChR treated with 3.0μM, 10.0μM and 30.0μM were 64.5%, 69.1% and 78.4%, respectively. Compared with the control group and 58.2 % And 68.3% have significantly increased, showing the phenomenon of G1 arrest. The results showed that dFMAChR could significantly inhibit the growth of human hepatocellular carcinoma xenografts, and the inhibition rates of dFMAChR at 20, 40 and 80 mg / kg on the xenografts in nude mice were 40.17% and 47.41 % And 66.81%. Conclusion: dFMAChR has the therapeutic effect on human liver cancer.