JNJ-7706621对阿霉素耐药乳腺癌细胞生长的抑制作用研究  

Anti-proliferative effect of JNJ-7706621 on adriamycin-resistant breast cancer cells

作　　者：谢闺娥[1] 杜晶春[1] 徐霞[1] 

机构地区：[1]广州医科大学金域检验学院,广东广州510182

出　　处：《临床和实验医学杂志》2017年第11期1061-1064,共4页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金资助项目(编号:81101682);广东省科技计划项目(编号:2014A020212015)

摘　　要：目的研究JNJ-7706621对人阿霉素耐药MCF-7/ADR乳腺癌细胞生长的作用。方法采用MTT试验检测JNJ-7706621对MCF-7/ADR耐药细胞生长的影响;采用TUNEL染色试验分析JNJ-7706621对MCF-7/ADR耐药细胞凋亡的激活作用;Caspase酶活性检测分析JNJ-7706621处理后,MCF-7/ADR细胞中Caspase-8、Caspase-9活化程度;应用流式细胞周期分析检测JNJ-7706621对MCF-7/ADR耐药细胞周期的影响。结果 JNJ-7706621能有效抑制阿霉素耐药细胞MCF-7/ADR的生长,并呈现明显的浓度依赖性,作用48 h的IC50仅为0.83μmol/L。2μmol/L JNJ-7706621作用24 h后,TUNEL染色阳性的MCF-7/ADR细胞比率较对照组显著升高,差异具有统计学意义(P<0.05);MCF-7/ADR细胞中Caspase-8、-9酶活性均显著升高,差异亦具有统计学意义(P<0.05)。在1μmol/L JNJ-7706621作用24 h后,G2/M期细胞比率由对照(7.1±1.3)%升高至(23.8±3.1)%,差异具有统计学意义(P<0.05)。结论 JNJ-7706621能同时激活内外源性凋亡途径,诱导MCF-7/ADR细胞凋亡的发生,并将MCF-7/ADR细胞周期阻滞在G2/M期,从而对阿霉素耐药MCF-7/ADR细胞的生长发挥有效抑制作用。Objective To investigate the effect of JNJ - 7706621 on the growth of adriamycin - resistant MCF - 7/ADR breast cancer cells. Methods The effect of JNJ - 7706621 on the growth of adriamycin - resistant MCF - 7/ADR cells was determined by MTT assay. The effect of JNJ - 7706621 on apoptosis in MCF - 7/ADR breast cancer cells was evaluated by TUNEL staining, and the activity of Caspase - 8 and Caspase - 9 was quantified by enzymatic activity assay. The effect of JNJ - 7706621 on cell cycle progression was analyzed by flow cytometry analysis. Results After treatment with JNJ - 7706621 for 48 h, MCF - 7/ADR cells displayed markedly inhibited growth in a dose - dependent man-ner, and calculated IC50 was 0. 83 μmol/L. The numbers of apoptotic MCF - 7/ADR cells, as revealed by TUNEL staining, significantly in-creased after JNJ - 7706621 treatment （ P 〈 0. 05 ） . The enzymatic activity of Caspase - 8 and Caspase - 9 markedly increased after JNJ - 7706621 treatment （ P 〈0.05） . JNJ - 7706621 treatment caused an increase of cells in G2/M phase from （7 .1 ±1.3）% to （23.8 ±3.1）% （ P 〈0. 05） . Conclusion These data demonstrates that JNJ -7706621 induces apoptosis through both intrinsic and extrinsic apoptotic pathways, in the meanwhile, JNJ-7706621 induces G2/M cell cycle arrest in MCF-7/ADR cells, and consequently suppress the growth of adriamycin - resistant MCF -7/ADR breast cancer cells.

关 键 词：乳腺癌细胞 阿霉素耐药 JNJ-7706621 MCF-7/ADR 凋亡 细胞周期 

分 类 号：R96[医药卫生—药理学]