胃癌耐药细胞特异性结合小肽对多药耐药的影响  

MDR-reversing effect of short peptide binding specifically to multidrug-resistant gastric cancer cells

作　　者：王鹏[1] 丁杰[1] 林涛[1] 韩霜[1] 曹珊珊[1] 葛伏林[1] 安广群[1] 李荣[1] 雷婷[1] 白飞虎[1] 樊代明[1] 

机构地区：[1]第四军医大学西京医院消化病研究所肿瘤生物学国家重点实验室,西安市710032

出　　处：《中华肿瘤杂志》2007年第4期258-261,共4页Chinese Journal of Oncology

摘　　要：目的 研究环九肽（SY1）与胃癌耐药细胞（SGC7901／VCR）的结合特性及其对胃癌耐药性的逆转作用。方法 将细胞分为SGC7901和SGC7901／VCR2组培养。以无关噬菌体、阴性噬菌体为对照组，用免疫荧光技术检测含有SY1的阳性噬菌体与SGC7901／VCR的结合特性；通过体外药敏试验（MTT）分析含有SY1的阳性噬菌体和化学合成的SY1对SGC7901／VCR耐药性的改变；应用流式细胞仪检测在SY1作用下SGC7901／VCR细胞内阿霉素（ADM）的蓄积和储留。结果 （1）免疫荧光分析的结果显示，含有SY1的阳性噬菌体能够结合于SGC7901／VCR的膜表面，而不与亲本细胞SGC7901结合，无关噬菌体和阴性噬菌体均不与SGC7901／VCR结合，表明SY1可与SGC7901／VCR特异性结合。（2）MTT试验结果显示，在含有SY1的阳性噬菌体及化学合成的SY1的作用下，SGC7901／VCR的存活率显著降低（P〈0．05），其对长春新碱的耐药性降低。（3）在化学合成的SY1作用下，SGC7901／VCR细胞内ADM的储留蓄积高于对照组（P〈0．05）。结论 利用环七肽库差减筛选得到的环九肽SY1不仅能与SGC7901／VCR特异性结合，而且可部分逆转其对长春新碱的耐药性。这可能为胃癌多药耐药的逆转提供新思路。Objective To investigate the binding effect of the short peptide SY1 to the multidrug- resistant gastric cancer cell line SGC7901/VCR cells and its reversing effect on those cancer cells. Methods The cultured cells were divided into two groups named SGC7901 and SGC7901/VCR. The SGC7901/VCR group was co-cultured with vincristine （VCR）. SY1 was obtained from cyclic 7-mer peptide library by differential screening. Immunofluorescence technique was used to detect the capacity of SYl-containing positive phage specifically binding to SGC7901/VCR cells, compared with that of the negative phage and unrelated phage. MTT assay in vitro was performed to analyze the alteration of drug resistance of SGC7901/ VCR cells, using the positive phages and the chemically synthesized SY1 peptide. Flow cytometry assay was performed to detect the accumulation and retention of adriamycin （ADM） in the SGC7901/VCR cells. Results Immunofluorescence analysis showed that the SYl-containing positive phages could bind to the SGC7901/VCR cell surface but not to its parent cell line SGC7901 cells. The unrelated phage and negative phage did not bind to SGC7901/VCR cells. These results indicated that SY1 could specifically bind to SGC7901/VCR cells. MTY assay in vitro showed that the survival rate of SGC7901/VCR cells was reduced considerably by the positive phages and the chemically synthesized SY1 peptide（ P 〈0.05）, indicating that SY1 enhanced the sensitivity of SGC7901/VCR cells to chemotherapeutic drug VCR. Flow-cytometric detection showed that SY1 enhanced the accumulation of ADM in the SGC7901/VCR cells, compared with that of the negative phages and the unrelated phages （ P 〈 0.05）. Conclusion SY1 not only is able to bind to SGC7901/VCR cells specifically, but also can partly reverse the resistance of SGC7901/VCR cell line to chemotherapeutic drug VCR. Those findings might be important to open a new approach to reverse the gastric cancer MDR.

关 键 词：胃肿瘤 SGC7901/VCR细胞 逆转耐药 短肽 

分 类 号：R686[医药卫生—骨科学]