蜂毒素与化疗药物的协同作用及其可能机制的实验研究  

Synergistic Interaction between Melittin and Chemotherapeutic Agents and Their Possible Mechanisms:an Experimental Research

作　　者：王瑞平[1] 黄舒然[2] 周锦勇[1] 邹玺[1] 

机构地区：[1]江苏省中医院肿瘤科,南京210029 [2]南京中医药大学第一临床医学院,南京210046

出　　处：《中国中西医结合杂志》2014年第2期224-229,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：江苏省六大高峰人才项目(No.WS037);江苏省中医药管理局领军人才项目(No.LJ200908);江苏高校优势学科建设工程资助项目(PAPD)

摘　　要：目的分别观察蜂毒素联合5-氟尿嘧啶（5．Fu）、顺铂（DDP）、多西紫杉醇（TXT）抗人胃癌细胞株BGC-823增殖的效果，并初步探讨其作用机制。方法运用中效原理进行统计分析，绘制5-Fu、DDP和TXT单药及分别与蜂毒素联合用药对该肿瘤细胞生长的剂量一效应曲线，确定联合用药时对肿瘤细胞的效应（FA）与合用指数（CI）的关系，判定药物间的相互作用。运用实时荧光定量PCR法检测蜂毒素分别联合5．Fu、DDP和TXT作用人胃癌细胞株BGC．823后对化疗药物相关基因表达的改变。结果（1）在一定的浓度范围内蜂毒素单药与3种化疗药物单药均对BGC-823细胞显示出了明显的生长抑制效果。（2）蜂毒素联合5-Fu作用于BGC-823细胞时，FA在0．35～0．75时，CI〈1。蜂毒素联合DDP作用于BGC-823细胞时，FA在O．55左右，CI=1；FA〈0．55，CI〈1。蜂毒素联合TXT作用于BGC-823细胞时，整个区间内均可见CI〈1。（3）蜂毒素分别与3种化疗药物联合作用于细胞后，化疗药物相关基因胸苷酸合成酶（thymidylatesynthetase，TS）、切除修复交叉互补基因1（excisionrepaircross—complementinggene1，ERCCl）、乳腺癌易感基因1（breastcancersusceptibilitygene1，BRCAl）、β微管蛋白Ⅲ（β—tubu-nⅢ，TUBB3）和微管相关蛋白tau（rrlicrotubule—associatedproteintau，MAPT）的表达明显低于空白对照组（P〈0．01）。结论蜂毒素具有增强5．Fu、DDP、T）（T对胃癌细胞BGC-823生长抑制效果的协同作用，其作用机制可能与下调化疗相关基因的表达有关。Objective To evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms. Methods Median effect anal- ysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the rela- tionship between fraction affected （FA） and the combination index （CI） acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC4323 cells with or without treatment were measured by real-time fluorescent quantitative PCR. Results （1） Both melittin and chemotherapeu- tic agents inhibited the growth of BGC-823. （2） For BGC-823 cells were acted by 5-Fu ＋ melittin, when FA ranged between 0.35 -0.75, CI was less than 1. For BGC-823 cells were acted by DDP ＋ melittin, when FA ranged 0.55 or so, CI =1 ; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT ＋melittin, CI less than 1 could be seen in the whole interval. （3） After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase （TS）, excision repair cross-complementing gene 1 （ERCC1）, breast cancer susceptibility gene 1 （BRCA1）, β-tubulin Ⅲ （TUBB3）, and microtubule-associated protein tau （MAPT）. Conclusions Melittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might beassociated with down-regulating chemotherapeutic agent-associated genes.

关 键 词：蜂毒素 人胃癌细胞株BGC-823 协同作用 实时荧光定量PCR 化疗药物相关基因 

分 类 号：R735.2[医药卫生—肿瘤]