CXCL12/CXCR4大肠癌细胞放射敏感度影响的实验研究
投稿时间:2017-02-08  修订日期:2017-03-10  点此下载全文
引用本文:孟祥宇,汪大伟,赵明,朱兴业.CXCL12/CXCR4大肠癌细胞放射敏感度影响的实验研究[J].医学研究杂志,2017,46(11):66-71
DOI: 10.11969/j.issn.1673-548X.2017.11.017
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作者单位E-mail
孟祥宇 150001 哈尔滨医科大学附属第一医院普外科  
汪大伟 150001 哈尔滨医科大学附属第一医院普外科  
赵明 150001 哈尔滨医科大学附属第一医院普外科 labixiaoxinmxy@163.com 
朱兴业 150001 哈尔滨医科大学附属第一医院普外科  
基金项目:中国博士后科学基金资助项目(2012M520769)
中文摘要:目的 研究CXCL12/CXCR4对大肠癌细胞放射敏感度的影响。方法 HCT116细胞系进行培养和分组,对其进行外源性CXCL12、AMD3100及CXCL12+siSurvivin处理在放射治疗下对其细胞存活分数、LDH、caspase-3,caspase-9进行检测。结果 外源性CXCL12处理减弱了放射诱导的细胞存活分数下降和细胞死亡的增加,抑制CXCR4促使大肠癌细胞对放射更敏感。CXCL12/CXCR4对细胞存活起关键作用,通过外源性CXCL12处理可逆转放射促使的Bax的表达和caspase-3和caspase-9的活性。在放射条件下抑制CXCR4可使细胞凋亡增强。此外,外源性CXCL12处理增加Survivin的表达,CXCL12对放射诱导的细胞凋亡的抑制作用是由Survivin的表达而实现。结论 CXCL12/CXCR4通过Survivin的表达在放射中保护结肠癌细胞,这意味着一个放射在大肠癌治疗应用的重要潜在机制。
中文关键词:CXCL12  凋亡  大肠癌  抗辐射  Survivin
 
Experimental Study of the Effect of CXCL12/CXCR4 on the Radiation Sensitivity of Colorectal Cancer Cells
Abstract:Objective To test the hypothesis that CXCL12/CXCR4 axis is closely related to the sensitivity to radiotherapy in colorectal cancer cells.Methods CT116 cell lines were cultured and treated with exogenous CXCL12, AMD3100 and CXCL12+siSurvivin. The cell Survival fractions, LDH, Caspase3 and Caspase9 were detected under the radiation therapy.Results We found that decreased cell Survival fractions and the increase of cell death induced by radiotherapy were attenuated by CXCL12 treatment, and inhibition of CXCR4 promoted colorectal cancers cell more sensitive to radiotherapy. We also examined the critical roles of CXCL12/CXCR4 in cell survival and found that radiotherapy facilitated the expression of Bax and activation of caspase-3 and caspase-9, which was reversed by CXCL12 treatment. Cell apoptosis was enhanced by inhibition of CXCR4 under conditions of radiotherapy. Furthermore, treatment with CXCL12 resulted in the increased expression of survivin and the inhibitory effects of CXCL12 on radiotherapy-induced apoptosis were mitigated by survivin knockdown.Conclusion These results indicate that CXCL12/CXCR4 protects colorectal cancer cells against radiotherapy via survivin, implying an important underlying mechanism of resistance to radiotherapy in the treatment of colorectal cancer.
keywords:CXCL12  Apoptosis  Colorectal cancer  Radioresistance  Survivin
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