bFGF反义寡核苷酸增强鼠黑色素瘤B16细胞化疗药物敏感性研究  

Antisense Phosphorothioate Oligonucleotides Targeting bFGF Enhanced Chemosensitivity in Mouse Melanoma B16 Cells

作　　者：黄红亮[1] 王宏[1] 唐勇[1] 邓宁[1] 杨红宇[1] 向军俭[1] 

机构地区：[1]暨南大学分子免疫与抗体工程中心,广东广州510632

出　　处：《现代生物医学进展》2007年第10期1477-1480,共4页Progress in Modern Biomedicine

基　　金：中国博士后科学基金(20060390735)资助

摘　　要：目的:研究bFGF反义硫代寡核苷酸增强肿瘤细胞对化疗药物敏感性作用。方法:设计、合成bFGF寡核苷酸,用聚乙烯亚胺(polyemyleneimine,PEI)介导bFGF反义硫代寡核苷酸转染入黑色素瘤B16细胞,MTT法检测bFGF反义硫代寡核苷酸及其与化疗药物联合处理后的细胞增殖率;半定量RT-PCR测定bFGF反义硫代寡核苷酸转染后细胞中bFGF mRNA水平;流式细胞仪分析bFGF反义硫代寡核苷酸诱导的细胞凋亡。结果:bFGF反义硫代寡核苷酸对B16细胞增殖的抑制率为64.8%,且呈剂量依赖效应。B16细胞中bFGF mRNA被bFGF反义硫代寡核苷酸显著降低,为对照细胞的57.9%,且bFGF反义硫代寡核苷酸诱导B16细胞凋亡,凋亡率为41.8%。bFGF反义硫代寡核苷酸转染能显著增强B16细胞对阿霉素、5-氟脲嘧啶及顺铂的敏感性,非特异性硫代寡核苷酸不影响阿霉素、5-氟脲嘧啶及顺铂抑制B16细胞增殖。结论:bFGF反义硫代寡核苷酸显著增强B16细胞的化疗敏感性,表明其可协同化疗药物用于治疗肿瘤。Objective： To detect whether a specific antisense phosphorothioate oligonucleotide targeting bFGF enhance chemosensitivity of carcinomas. Methods： bFGF-specific antsense phosphorothioate oligonuleotides were transfected into mouse melanoma B 16 cell lines with jetPEI （polyethyleneimine）. The relative cell proliferation was analyzed by MTT assay, bFGF mRNA level was evaluated by semi-quantitative RT-PCR, and apoptosis of the B 16 cells induced by antisense phosphorothioate oligonucleotides targeting bFGF was analyzed by flow cytometry, Cell proliferation was then analyzed after treatment with both bFGF-specific antsense phosphorothioate oligonuleotides and chemotherapeutic drugs by MTT assay, Results： bFGF-specific antisense phosphorothioate oligonuleotides inhibited the growth of B16 cells by 64.8% in a dose and time-dependent manner, significantly reduced the bFGF mRNA level to 57.9% of control cells, and induced apoptosis by 41.8%. Compared to nonspecific phosphorothioate oligonuleotides, bFGF-specific antisense phosphorothioate could significantly enhance chemosensitivity of B 16 cells to adriamycin （ADM）, 5-fluorouracil （ 5-FU）, and cis-diaminodichloroplatin （DDP）. Conclusion： bFGF-specific antisense phosphorothioate oligonucleotides have therapeutic effects on mouse melamoma B16 cells, and are a potential antitumor agent combined with chemotherapeutic drugs.

关 键 词：BFGF 肿瘤 反义寡核苷酸 药物敏感性 

分 类 号：R73-361[医药卫生—肿瘤]