6,8-二-三氟甲基-5-羟基-7-乙酰基白杨素的抗肿瘤作用

目的　研究 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素的抗肿瘤作用及机制。方法　采用MTT比色法检测白杨素及白杨素乙酰化、卤化、三氟甲基化衍生物体外抗肿瘤活性 ;小鼠Lewis肺癌移植瘤模型观察目标化合物 (6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素 )体内抗肿瘤作用 ;PI染色流式细胞术分析 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素对人胃癌(SGC 790 1 )细胞周期的影响。结果　白杨素及白杨素乙酰化、卤化、三氟甲基化衍生物对体外培养人胃癌 (SGC 790 1 )细胞 ,人急性粒细胞性白血病 (HL 6 0 )细胞和人结肠癌 (HT 2 9)细胞具有抑制增殖作用 ;以 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素作用最强 ,其对SGC 790 1细胞 ,HT 2 9细胞和HL 6 0细胞的IC50 分别是 2 5 1 ,1 96和 0 1 8μmol·L-1 。 6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素对小鼠Lewis肺癌皮下移植原发瘤及自发性肺转移具有抑制作用 ,呈剂量依赖关系。6 ,8 二 三氟甲基 5 羟基 7 乙酰基白杨素 (1～ 2 μmol·L-1 )能使SGC 790 1细胞周期阻滞于G1 期。结论　 6 ,8 二 三氟甲基 5 羟基 7 乙酰白杨具有抗肿瘤作用 ,其机制可能与使细胞周期G1 期阻滞相关

The Antitumor Effect of 6,8-ditrifluoromethyl-5-hydroxyl-7-acetoxy chrysin

AIM To study the antitumor effect and mechanism of 6, 8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin. METHODS The cytotoxic effect of chrysin and chrysin derivations,prepared by acetylation, halogenation,and trifluoromethylation, were determined by 3 4,5 dimethylthiazol 2 yl]5 diphenyl tetrazolium bromid(MTT) assay in vitro; The antitumor activity of target compound (6, 8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin) was measured in Lewis lung carcinoma transplanted into mouse C57BL/6N in vivo ; After treatment with 6, 8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin, the influence on cell cycle of human gastric adenocarcinoma ( SGC 7901) cells was detected by flow cytometry(FCM). RESULTS chrysin and chrysin derivations,prepared by acetylation, halogenation, trifluoromethylation significantly suppressed proliferation of human gastric adenocarcinoma(SGC 7901)cells,human acute Granulocytic leukemia(HL 60) cells and human colorectal adenocarcinoma(HT 29) cells in vitro . The 6,8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin was the strongest potency among them, its IC 50 of SGC 7901, HT 29 and HL 60 cells was 2 51, 1 96 and 0 18 μmol·L -1 respectively. The 6,8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin significantly inhibited the primary tumor subcutaneously transplanted and spontaneous lung metastasis of mouse Lewis lung carcinoma in dose dependent manner. After treatment with 6, 8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin, cell cycle analysis of SGC 7901 cells showed a G1 phase arrest. CONCLUSION 6,8 ditrifluoromethyl 5 hydroxyl 7 acetoxy chrysin posseses antitumor effect in vitro and in vivo, its mechanism might be associated with G1 phase cell cycle arrest.