【摘要】 联合应用靶向ErbB1的抗肿瘤药吉非替尼与传统化疗药紫杉醇,观察ErbBs高表达胃癌细胞的生长抑制作用及对ErbBs的影响.采用MTT法检测两药不同比例联合应用时对ErbBs高表达胃癌细胞的抑制作用,在此基础上通过计算CI值(Combination Index Value),考察两药合用于ErbBs高表达胃癌细胞株时的相互作用关系(协同,相加或拮抗).发现在两药浓度比例为330∶1,联合抑制率在60%~80%时,能够协同抑制ErbBs高表达胃癌细胞.并进一步探讨其可能的机制,通过Western Blot法检测药物作用对ErbBs,磷酸化ErbBs以及下游信号通路中(如PI3K-Akt信号途径)信号分子(Akt/磷酸化Akt)表达的影响.最终导致细胞死亡增多,通过DNAladder、Hochest33342染色、及检测凋亡相关蛋白的表达情况进一步确证协同促进细胞凋亡的作用.结果表明两药适宜配比可协同抑制ErbBs高表达胃癌细胞.更多还原

【Abstract】 The antitumor activites combinated gefitinib targeted EGFR with the traditional chemotherapeutic drug paclitaxel are evaluateed by MTT assay.Different proportion of the two drugs is used against gastric cancer cells with ErbBs over-expression to determine their interactions(synergism,antagonism or addition).When the concentration proporation of the two drugs is in 330∶1 and the overall inhibitory ratio is 60%～80%,the interaction of the two drugs showed favorable synergism as determined by combination index(CI) analysis.Western Blot analysis is used to find the expression of ErbBs,phosphorylated ErbBs and signaling molecules in the downstream signaling pathway related to ErbBs,such as Akt/phosphorylated Akt.Apoptosis is potentiated by the co-admimistration compared with the single treatment of the respective drug which is confirmed by analyses of DNA ladder,Hochest 33342 staining and the expressions of apoptosis-related proteins.更多还原