摘要
目的:探讨以c-erbB2 mRNA为靶点的反义寡脱氧核苷酸(ASODN)联合紫杉醇对乳腺癌SK-Br-3细胞的抑制作用.方法:实验分为7组:ASODN组,紫杉醇组,赫赛汀组,表阿霉素组,ASODN+紫杉醇组,赫赛汀+紫杉醇组,表阿霉素+紫杉醇组.分别处理乳腺癌SK-Br-3细胞72 h,MTT法测定细胞抑制率,中效原理判定药物联合应用的效果,WesternBlot检测细胞c-erbB2,Bcl-2蛋白表达水平.结果:各组中SK-Br-3细胞的抑制率均随药物浓度的增加而增大;紫杉醇的中效浓度紫杉醇组为0.14 umol/L;ASODN+紫杉醇组为0.07umol/L,其合用指数(CI)<1,为协同作用.ASODN+紫杉醇组c-erbB2,Bcl-2蛋白表达明显低于紫杉醇组,两组相比较,差异具有统计学意义(P<0.05).结论:ASODN可明显增强紫杉醇对乳腺癌SK-Br-3细胞的抑制效应,可明显降低紫杉醇的用药量.
Abstract
AIM : To explore the inhibitory effect on human breast cancer SK-Br-3 cells treated with c-erbB2 antisense oli-godeoxynucleotide(ASODN) combined with taxol. METHODS: SK-Br-3 cells were treated with ASODN, taxol, herceptin, Epiru-bicin, ASODN combined with taxol, herceptin combined with taxol, and Epirubicin combined with taxol for 72 h respectively. The inhibitory effect was detected by MTT assay. The drug's interactional effect was determined by median-effect principle. The expression of c-erbB2 and Bcl-2 was detected by western blot in SK-Br-3 cells. RESULTS: The inhibition ratio of each group increased while the increased concentration of drugs used. The median concentration of taxol was 0.14 μmol/L in taxol group and 0.07 μmol/L in ASODN combined taxol group respectively. The combination index(CI) of ASODN combined with taxol group was always less than 1, indicating that there was some synergistic effects between ASODN and taxol. The expression of c-erbB2 and Bcl-2 proteins was significantly lower in ASODN + taxol group than that in other groups and the difference was statistical significance (P<0.05). CONCLUSION: ASODN significantly enhances the inhibitory effect of taxol on human breast carcinoma SK-Br-3 cells and markedly lowers the taxol's dosage of administration.
基金项目
国家自然科学基金(30070230)
重庆市科学技术委员会科技攻关计划(CSTC)
重庆市科学技术委员会科技攻关计划(2007BB5305)