南方红豆杉水提物与厄洛替尼联用抑制裸鼠A549肺癌移植瘤生长及其机制探析  

Study on Inhibitory Effect of Aqueous Extract of Taxus Chinensis var. mairei Combined Erlotnib on A549 Xenograft in Nude Mice and Its Mechanism

作　　者：崔庆丽[1,2,3] 叶平[4] 舒琦瑾[3] 邵梅[3,5] 

机构地区：[1]郑州大学附属肿瘤医院 [2]河南省肿瘤医院中西医结合科,郑州450008 [3]浙江中医药大学附属第一医院肿瘤科,杭州310006 [4]浙江省立同德医院生殖免疫科,杭州310000 [5]中国人民解放军第八十一医院消化科,南京210002

出　　处：《中国中西医结合杂志》2015年第5期572-577,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省自然基金项目(No.Y2081051);浙江省中医药管理局重点项目(No.2009ZA003)

摘　　要：目的研究南方红豆杉水提物联合厄洛替尼抑制裸鼠A549移植瘤生长及其机制。方法建立荷瘤裸鼠模型,随机分为低剂量厄洛替尼组(A组)、标准剂量厄洛替尼组(B组)、低剂量厄洛替尼联合南方红豆杉水提物组(C组)、标准剂量厄洛替尼联合南方红豆杉水提物组(D组)、南方红豆杉水提物组(E组)、对照组(F组),每组12只,接种24 h后连续给药7周,采血1 m L、取瘤组织,计算抑瘤率,金氏公式分析两药联合作用。Real-time PCR和ELISA法分别检测表皮生长因子(EGFR)、环氧化酶(cyclooxygenase,COX)-2及B细胞淋巴瘤-2(B cell lymphoma-2,BCL-2)mRNA和蛋白水平。结果与F组比较,B^E组裸鼠移植瘤瘤重均明显降低,差异有统计学意义(P<0.05,P<0.01)。低剂量厄洛替尼和南方红豆杉水提物的金氏值为0.92,标准剂量厄洛替尼和南方红豆杉水提物的金氏值为0.96,均为两药合用单纯相加。与F组比较,D、E组EGFR mRNA水平、A^E组COX-2 mRNA水平及B^D组Bcl-2 mRNA水平均明显降低,B^E组COX-2蛋白水平及C、D组Bcl-2蛋白水平均明显降低,差异有统计学意义(P<0.05,P<0.01)。结论南方红豆杉水提物与低剂量厄洛替尼、标准剂量厄洛替尼均有相加抑瘤作用,两者联合抑瘤作用机制可能与下调COX-2和Bcl-2 mRNA及蛋白表达水平有关。Objective To study the effect of aqueous extract of Taxus chinensis var. mairei （AETC） combined Erlotnib on the growth of A549 xenograft in nude mice and its mechanism. Methods The xenograft model in nude mice was established by inoculating A549 cells subcutaneously. BALB/c nude mice bearing A549 xenograft were randomly divided into six groups, i.e., the low dose Erlotinib group （A）, the standard dose Erlotnib group （B）, the low dose Erlotinib combined AETC group （C）, the standard dose Erlotnib combined AETC group （D）, the AETC group （E）, the control group （F）, 12 in each group. Different medication was performed for 7 successive weeks after 24 h. One mL blood was withdrawn and tumor tissues taken. The tumor inhibition rate was calculated. The combined effect was analyzed by Jin＇s Formula [ Q = Ea ＋ b/（ Ea ＋ Eb-Ea x Eb） 1. mRNA and protein expression levels of epidermal growth factor receptor （EGFR）, cyclooxygenase-2 （COX-2）, and B cell lymphoma-2 （Bcl-2） in xenografts were detected using real-time RT-PCR and ELISA. Results Compared with Group F, the xenograft weight was obviously lowered in Group B-E （P 〈0.05,P 〈0.01 ）. The q value was 0.92 in Group C and 0.96 in Group D, which was obtained by simple adding of the two drugs. Compared with Group F, EG- FR mRNA expression in Group D and E, COX-2 mRNA expression in Group A-E; Bcl-2 mRNA expression in Group B-D; COX-2 protein expression in Group B-E; Bcl-2 protein expression in Group C and D were obviously lowered with statistical difference （P 〈0.05,P 〈0.01 ）. Conclusions AETC combined low dose and standard dose Erlotinib had synergistic effect on tumor inhibition. Its mechanism might be associated with down-regulating mRNA and protein expression levels of COX-2 and Bcl-2.

关 键 词：南方红豆杉 厄洛替尼 A549肺癌 移植瘤 抑制作用 

分 类 号：R734.2[医药卫生—肿瘤]