摘要
目的:研究新型水溶性开环喜树碱衍生物XY-8的体内外抗肿瘤活性,并初步探讨其抗肿瘤机制。方法:MTT法测定XY-8对15种肿瘤细胞株的细胞增殖活性的影响;选用小鼠H22肝癌以及人胃腺癌SGC-7901裸小鼠移植瘤模型检测XY-8的体内抗肿瘤活性;FCM分析XY-8对癌细胞的影响,初步考察其抗肿瘤作用机制。结果:15种肿瘤细胞株中,XY-8对8种有很强的抗增殖作用(IC50<1μmol·L-1),对6种有较强作用(1μmol.L-1≤IC50<10μmol·L-1),对1种无效;体内试验,XY-8给药2.5,5,10mg·kg-1均能显著抑制肿瘤生长;FCM分析结果显示,XY-8在0.25μmol·L-1浓度下即能有效将肿瘤细胞阻滞于G2/M期,抑制S期。结论:XY-8具有较好的体内外抗肿瘤活性,对肿瘤细胞的细胞周期阻滞作用是其抗肿瘤作用的重要机制之一。
AIM： To evaluate the antitumor activity of XY-8, a novel water-soluble camptothecin analogue developed on the concept of DNA topoisomerase I （Topo I ） inhibition and characterized by an open E-ring. METHODS： We investigated the growth inhibitory effects of XY-8 and 10-OH-camptothecin, used as a reference compound, in a panel of human tumor cell lines of various tumor types. We explored the antitumor efficacy in mice H22 hepatoma model and a human tumor xenograft, using intravenous injection. And the study on cell cycle arrest effect of XY-8 was also included to explore its antitumor mechanism. RESULTS： XY-8 showed a potent antiproliferative activity with comparable effects in majority of 15 tested cell lines, presumably as a consequence of the efficiency of the G2-phase checkpoint. Only SMMC-7721 cells were less sensitive. XY-8 produced a remarkable antitumor effect in examined models. CONCLUSION： These results provide evidence that XY-8 is a promising novel camptothecin analogue with potent antitumor activity in vitro and in vivo, and that it may be necessary to reevaluate the role of E-ring-opened camptothecin analogues.
出处
《中国天然药物》
SCIE
CAS
CSCD
2007年第4期297-300,共4页
基金
江苏省药效研究和评价服务中心资助(NoBM2005103)~~
