| 引用本文: | 徐烨,崔焌辉,陈诚豪,都志军.MiR-24反义核酸通过BIM-Smac/Diablo途径促进多柔比星对结肠癌细胞的凋亡诱导效应[J].中国现代应用药学,2016,33(2):175-181. |
| XU Ye,CUI Junhui,CHEN Chenghao,DU Zhijun.Antisensenucleic Acids of miR-24 Promoted the Doxorubicin-induced Apoptosis via BIM-Smac/DIABLO Pathway in Colon Cancer[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(2):175-181. |
|
| 摘要: |
| 目的 探讨miR-24在结肠癌中发挥的作用并研究其是否和多柔比星的体外治疗有关。方法 用RT-qPCR法检测miR-24在结肠癌患者血浆中及结肠癌细胞系中的表达水平。MTT法检测miR-24反义核酸对多柔比星杀伤结肠癌细胞能力的影响。利用生物信息学、定量PCR及western blot法验证miR-24是否调节结肠癌细胞BIM的表达。运用JC-1染色、Annexin V染色及western blot法研究miR-24反义核酸影响多柔比星疗效的信号通路。结果 结肠癌患者血浆及结肠癌细胞系中miR-24表达水平显著升高。miR-24反义核酸可显著增强多柔比星对SW480细胞的杀伤活性。定量PCR及western blot实验表明miR-24的靶基因可能为BIM。miR-24反义核酸联合多柔比星可引起SW480细胞线粒体膜电位的丧失并诱导线粒体内Smac/DIABLO的释放，进而引起caspase-3的活化和凋亡的发生。转染BIM siRNA后miR-24反义核酸联合多柔比星对SW480细胞的凋亡诱导效应显著降低。结论 MiR-24反义核酸通过BIM-Smac/Diablo途径促进多柔比星对结肠癌细胞的凋亡诱导效应。 |
| 关键词: miR-24 BIM Smac/DIABLO SW480 多柔比星 |
| DOI： |
| 分类号: |
| 基金项目: |
|
| Antisensenucleic Acids of miR-24 Promoted the Doxorubicin-induced Apoptosis via BIM-Smac/DIABLO Pathway in Colon Cancer |
|
XU Ye, CUI Junhui, CHEN Chenghao, DU Zhijun
|
|
Anus-intestines Department, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
|
| Abstract: |
| OBJECTIVE To investigate the role of miR-24 in doxorubicin treatment in colon cancer. METHODS MiR-24 levels in plasma and colon cancer cell lines were detected by RT-qPCR assay. MTT assay was performed to evaluate the effect of antisensenucleic acids of miR-24 (anti-miR-24) to doxorubicin-induced cell death in SW480 cells. Bioinformatics, quantitative PCR and western blot analysis were performed to determine whether the expression of BIM was regulated by miR-24. JC-1 staining, Annexin V staining and western blot analysis were performed to study the pathway of anti-miR-24 to increase the anti-tumor effect of doxorubicin. RESULTS The expression of miR-24 was up-regulated in colon cancer patients’ plasma and colon cancer cell lines. The anti-tumor effect of doxorubicin was significantly enhanced after the SW480 cells were transfected with anti-miR-24. The results of western blot and RT-qPCR assays indicated that the BIM gene was the target of miR-24. Furthermore, the apoptosis induced by anti-miR-24 plus doxorubicin was dependent on the dysfunction of mitochondrial membrane, leading to the release of Smac/DIABLO from the mitochondrial and activation of caspase-3 in SW480 cells. CONCLUSION anti-miR-24 promoted the doxorubicin-induced apoptosis via BIM-Smac/DIABLO pathway in colon cancer. |
| Key words: miR-24 BIM Smac/DIABLO SW480 doxorubicin |
