敏感性评价中的应用斑马鱼肿瘤异种移植模型在抗癌药

摘要

目的 应用人类肺癌、胃癌和肝癌细胞斑马鱼异种移植模型,分别评价5种临床常用抗癌药的体内敏感性.方法 分别建立斑马鱼肺癌A549、胃癌SGC-7901和肝癌HepG2异种移植模型,顺铂、紫杉醇、长春瑞滨、恩度和贝伐单抗设计3个剂量分别处理斑马鱼肺癌A549移植模型,紫杉醇、伊立替康、羟基脲、顺铂和5-氟尿嘧啶(5-fluorouracil,5-FU)设计3个浓度或剂量分别处理斑马鱼胃癌SGC-7901移植模型,阿霉素、吉西他滨、羟基脲、顺铂和5-氟尿嘧啶设计3个浓度或剂量分别处理斑马鱼肝癌HepG2移植模型.实验结束后,使用荧光显微镜进行体内肿瘤定量图像分析,计算药物对斑马鱼体内肿瘤生长抑制率,通过与模型对照组相比,分析是否具有统计学意义.结果 受试的抗肿瘤药物在斑马鱼肿瘤异种移植模型中均有效,并且基本都呈剂量依赖性.在抗肺癌A549药敏试验中,药效从高到低分别为贝伐单抗(65%)>顺铂(55%)>长春瑞滨(40%)>恩度(39%)>紫杉醇(27%);在抗胃癌SGC-7901药敏试验中,药效从高到底分别为羟基脲(46%)>5-FU(31%)=伊立替康(31%)>紫杉醇(26%)>顺铂(24%);在抗肝癌HepG2药敏试验中,药效从高到底分别为顺铂(64%)>羟基脲(56%)>吉西他滨(46%)>阿霉素(45%)>5-FU(38%).结论 斑马鱼肿瘤异种移植模型适合用于抗癌药体内药敏试验.%Objective To evaluate the sensitivity to 5 clinically commonly used anticancer drugs in vivo using the zebrafish xenotransplantation models of human lung cancer,stomach cancer,and liver cancer cells,respectively. Methods Zebrafish xenotransplantation models of A549 lung cancer cells,SGC-7901 stomach cancer cells and HepG2 liver cancer cells were established. The xenograft models of A549 cells were treated with three different doses of cis-platinum, paclitaxel, vinorelbine, endostar and bevacizumab, respectively. The SGC-7901 model was treated with three concentrations or doses of paclitaxel, irinotecan, hydroxyurea, cis-platinum and 5-fluorouracil, respectively. And the HepG2 model was treated with three concentrations or doses of adriamycin,gemcitabine,hydroxyurea,cis-platinum and 5-fluorouracil. The tumors were analyzed and quantified in vivo by fluorescence microscopy,and the inhibition rates of tumor growth with each drug were calculated and compared with the model control group for statistical significance. Results All of the tested anticancer drugs showed inhibitory effect on tumor cells in the zebrafish xenograft models with statistical significance in a dose-dependent manner. During the drug sensitivity test,the inhibition rate of bevacizumab on A549 lung cancer cells decreased in the order(65%)> cis-platinum(55%)> vinorelbine(40%)> endostar(39%)>paclitaxel(27%). As for the SGC-7901 stomach cancer cells, the tumor growth inhibition rate decreased in the order hydroxyurea(46%)> 5-FU(31%)= irinotecan(31%)> paclitaxel(26%)> cis-platinum(24%). And the therapeutic effect of cis-platinum on the HepG2 liver cancer cells decreased in the order(64%)> hydroxyurea(56%)>gemcitabine(46%)> adriamycin(45%)> 5-FU(38%). Conclusions Zebrafish xenotransplantation models of cancer cells are suitable for in vivo sensitivity test of anticancer drugs.