5-杂氮-2'-脱氧胞苷对乳腺癌MCF-7细胞实验性肺转移的影响  

Effect of 5-Aza-2′-deoxycytidine on experimental lung metastasis of breast cancer MCF-7 cells

作　　者：沈三弟[1] 吴爱国 邵国利[1] 

机构地区：[1]南方医科大学珠江医院普外科,广州市510282

出　　处：《实用医学杂志》2010年第18期3293-3296,共4页The Journal of Practical Medicine

基　　金：广东省科技计划项目基金资助项目(编号:2008B030301345)

摘　　要：目的:探讨5-杂氮-2′-脱氧胞苷(5-Aza-2′-deoxycytidine,5-Aza-CdR)对非浸润性人乳腺癌MCF-7细胞实验性肺转移的影响及可能的机制。方法:将MCF-7细胞分为对照组与5-Aza-CdR处理组,分别通过半定量RT-PCR(semi-quantitative RT-PCR,SqRT-PCR)与甲基化特异性PCR(methylation-specific PCR,MSP)方法检测两组细胞的CXC趋化因子受体-4(CXCR4)、乳腺癌转移抑制基因-1(BRMS1)的mRNA表达与启动子区甲基化状况。然后分别将两组细胞通过边缘尾静脉注射到BALB/c nu/nu裸鼠体内,5周后,用荧光定量RT-PCR(fluorescent quantitative RT-PCR,FqRT-PCR)检测裸鼠肺组织内的目的基因HPRT mRNA丰度。结果:处理组CXCR4mRNA表达明显上调(P<0.05),5-Aza-CdR使CXCR4启动子区甲基化的CpG岛1完全去甲基化;两组BRMS1mRNA表达无明显差异(P>0.05),BRMS1启动子区CpG岛B的非甲基化状态亦无明显改变。处理组裸鼠肺脏HPRT mRNA丰度高,转移癌组织较多。结论:5-Aza-CdR通过去甲基化机制上调了促转移基因CXCR4的表达,从而增强了MCF-7细胞实验性肺转移能力。Objective To investigate the effect of 5-Aza-2′-deoxycytidine （5-Aza-CdR） on experimental lung metastasis of noninvasive human breast cancer MCF-7 cells and its possible mechanism. Methods MCF-7 cells were divided into control group and 5-Aza-CdR-treated group. The expression of mRNA and promoter region methylation status of CXC chemokine receptor -4 （CXCR4） and breast cancer metastasis suppressor-1 （BRMS1） of the MCF-7 cells were evaluated by semi-quantitative RT-PCR （SqRT-PCR） and methylation-specific PCR （MSP） respectively. Then, the MCF-7 cells in both groups were injected into BALB / c nu / nu mice through lateral tail veins respectively. 5 weeks later, the mRNA abundance of the target gene hypoxanthine guanine phosphoribosyl transferase （HPRT） and internal control gene glyceraldehyde-3-phosphate dehydrogenase （GAPDH） in the lung tissues of the mice were evaluated by fluorescent quantitative RT-PCR （FqRT-PCR）. Results 5-Aza-CdR upgraded the expression of CXCR4 mRNA（P 0.05） and demethylated the methylated CpG island 1 in promotor, while the expression of BRMS1 mRNA （P 0.05） and the status of unmethylated BRMS1 CpG island B in promotor were not changed significantly. The abundance of the HPRT mRNA was higher and there were more metastatic carcinoma tissures in the lungs of mice in 5-Aza-CdR-treated group. Conclusion 5- Aza-CdR upgraded the expression of CXCR4 and promoted the experimental lung metastasis ability of breast cancer MCF-7 cells by demethylation mechanism.

关 键 词：乳腺肿瘤 5-杂氮-2′-脱氧胞苷 CXC趋化因子受体-4 乳腺癌转移抑制基因-1 基因甲基化 实验性转移 

分 类 号：R737.9[医药卫生—肿瘤]