苦参总黄酮体内外抗肿瘤作用实验研究

目的：考察苦参总黄酮（kushenflavonoids，KS—Fs）的体内外抗肿瘤作用。方法：采用甲基噻唑基四唑（methylthiazolyltetrazolium，MTT）比色法检测KS—Fs对多种肿瘤细胞株的生长抑制作用；构建S180肉瘤、H22肝癌和Lewis肺癌小鼠肿瘤模型和人非小细胞肺癌H460、食管癌Eca-109裸小鼠移植肿瘤模型，研究KS—Fs体内抗肿瘤作用；急性毒性试验考察KS—Fs的毒副作用。结果：KS—Fs和苦参酮（kurarinone，Kur）在体外有比苦参总碱（kushenalkaloids。KS—As）更强的细胞毒作用（半数抑制率：KSFs4．9～29．4〉g／ml，Kur2．0～13．1〉g／ml，KSAs〉200／lg／m1）。体内研究表明KSFs和Kur不仅能有效抑制小鼠H22肝癌、S180肉瘤、Lewis肺癌（瘤质量抑瘤率60％～80％），而且能显著抑制人非小细胞肺癌H460和人食管癌Eca109裸小鼠移植肿瘤的生长（瘤质量抑瘤率在41％～47％）。小鼠口服和静脉注射KS—Fs的最大耐受剂量分别大于2．8g／kg和750mg／kg，远远超过苦参碱（口服半数致死量为1．18g／kg），且无明显毒副作用。结论：研究表明KSFs或Kur是新颖的高效低毒的抗肿瘤候选药物。

Antitumor activities of kushen flavonoids in vivo and in vitro

OBJECTIVE: To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro. METHODS: Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5x10(5) or 5x10(6) tumor cells in the right flank, respectively. RESULTS: KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (< or = 1.18 g/kg). No adverse reactions were observed. CONCLUSION: These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.