苦参总黄酮体内外抗肿瘤作用实验探究.docVIP

苦参总黄酮体内外抗肿瘤作用实验探究 　 作者：孙明瑜, 左剑, 段继峰, 韩军, 范士明, 张炜, 朱丽芳, 姚明辉 【关键词】 苦参; 黄酮类; 抗肿瘤药; 小鼠 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 5×105 or 5×106 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 (≤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. Keywords: Sophora flavescens; flavones; antineoplastic agents; mice 苦参（Sophora flavescens Aiton）为豆科槐属植物，是中国传统常用中药之一，始载于《神农本草经》，列为中品，常用于治疗急、慢性炎症和癌症等疾病。苦参主要含有生物碱和黄酮两大类化学成分［1］。1992年以苦参碱和氧化苦参碱为主的苦参总碱注射液吗特灵［（92）卫药试字X-10（2）号］已作为抗肿瘤药批准上市。相对于苦参碱，苦参黄酮的研究较迟。现已从苦参根中分离出56种黄酮类化合物，其中大部分化合物的A环上存在异戊烯基侧链［2-14］。研究表明异戊烯基侧链黄酮有抗病原微生物、抗炎、抗肿瘤（体外）等生物活性［2-14］。 一系列从苦参中分离出的含异戊烯基侧链的苦参黄酮在体外对一些人肿瘤细胞株有细胞毒活性，例如人白血病HL-60［2］、K562，小鼠白血病L1210［10］，人乳腺癌MCF-7［11］，非小细胞肺腺癌A549，卵巢癌SKOV-3［12］、1A9［9］，皮肤黑素瘤SK-MEL-2，中枢神经系统肿瘤XF498，肠癌HCT［12］，子宫颈癌HeLa［10］，鼻咽上皮癌KB，KB-Vin（drug-resistant variant KB）等细胞株［10］。这些黄酮还可以抑制一些酶的活性，例如phospholipase Cγ1［7］，diacylglycerol acyltransferase［9，13］，tyrosinase［5，14］，testosterone 5α-reductase［6］，cGMP phosphodiesterase 5［8］。但苦参黄酮在体内是否有抑制肿瘤作用，目前国内外均没有相关报道。 本研究提取分离苦参总黄酮（kushen flavonoids, KS-Fs）和苦参酮（kurarinone, Kur），检测KS-Fs和Kur对肿瘤细胞增殖的影响，并比较KS-Fs与市售