斑蝥酸钠诱导RTP801表达促进结肠癌细胞HCT116凋亡  

Sodium Cantharidinate-induced RTP801 Expression Promotes Apoptosis of Colonic Cancer Cell Line HCT116

作　　者：张霞[1,2] 关洪全[2] 

机构地区：[1]中国医科大学肿瘤医院、辽宁省肿瘤医院内五科,沈阳110042 [2]辽宁中医药大学免疫与病原生物教研室,沈阳110847

出　　处：《中国医科大学学报》2016年第3期222-226,共5页Journal of China Medical University

摘　　要：目的探讨斑蝥酸钠注射液对结肠癌细胞凋亡的影响作用及分子机制。方法通过异硫氰酸荧光素(FITC)-右旋糖酐渗透实验观察终浓度为0.1、0.25、0.5、1、2μg/m L斑蝥酸钠注射液处理24 h后对HCT116细胞凋亡的影响;分别用real-time PCR和Western blot方法检测终浓度为0.1、0.25、0.5、1、2μg/m L斑蝥酸钠注射液处理24 h后对促凋亡基因DNA损伤修复基因(RTP801)表达的影响;运用低氧诱导因子1α(HIF-1α)质粒和HIF-1α-si RNA转染检测HIF-1α信号通路对RTP801的影响。结果斑蝥酸钠注射液诱导单层细胞渗透性增加,FITC-右旋糖酐渗透率增高。细胞受斑蝥酸钠注射液刺激后,RTP801的m RNA和蛋白水平上调,且都呈浓度依赖性。HIF-1α质粒转染后,RTP801蛋白表达增加;加入HIF-1α-si RNA,斑蝥酸钠注射液对RTP801的上调作用降低,且FITC-右旋糖酐渗透率下降。结论斑蝥酸钠通过HIF-1α途径增加RTP801的表达,诱导结肠癌细胞HCT116凋亡。Objective To investigate the impact of sodium cantharidinate on apoptosis of colonic cancer cell line HCT116 and explore its molecular mechanism. Methods HCT116 cells were treated with sodium eantharidinate with different concentrations of 0.1,0.25,0.5,1,2μg/mL for 24 h. The apoptosis of HCT116 cells was assessed by FITC （Huoreseeirl iso-thiocyanat）-Dextran permeability assay. RTPS01 expression was determined by real-time PCR and Western blot. The action of Hypoxia inducible factor-1 α （HIF-1 α ） signaling pathway was measured by HIF-1 a plasmids and HIF- 1 α- siRNA transfection assays. Results Sodium eantharidinate increased cell monolayer permeability and HTC - Dextran intiltration. Both of mRNA and protein levels of RTPS01 were up-regulated after sodium eantharidinate treatment in a dose-dependent manner. After HIF- 1 α plasmids transfection, RTPSO1 expression was increased markedly, while RTP801 and permeability up-regulations were both blocked by HIF- lot-siRNA in the presence of sodium cantharidinate. Conclusion Sodium cantharidinate increases RTP801 expression through HIF- 1 α pathway, which finally induce HCT116 cells apoptosis.

关 键 词：斑蝥酸钠 结肠癌 低氧诱导因子1Α DNA损伤修复基因 凋亡 

分 类 号：R735.3[医药卫生—肿瘤]