The radiosensitization effect of NS398 on esophageal cancer stem cell-like radioresistant cells
The radiosensitization effect of NS398 on esophageal cancer stem cell-like radioresistant cells
复制标题
NS398对食管癌干细胞样放疗细胞的放射增敏作用
DOI：
10.1111/j.1442-2050.2010.01138.x
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发表时间：
2011-05-01
影响因子：
2.6
通讯作者：
Hou, L.
中科院分区：
文献类型：
--
作者：
Che, S. -M.;Zhang, X. -Z.;Hou, L.
本研究旨在探讨放射抗性食管癌细胞的肿瘤干细胞特性及环氧合酶（考克斯）-2抑制剂NS 398对放射抗性食管癌细胞的放射增敏作用。采用分次照射法获得放射抗性食管癌细胞。克隆形成实验检测细胞的放射敏感性和克隆形成能力。甲基四氮唑比色法测定细胞活力。流式细胞仪检测细胞周期分布及凋亡情况。通过异种移植致瘤性试验研究致瘤性。逆转录聚合酶链反应或Western blot检测β-连环蛋白的表达水平。结果表明，Eca 109细胞经分次照射后，可获得抗辐射的Eca 109 R50 Gy细胞，其增殖能力、集落形成能力和体内致瘤能力是Eca 109细胞的40倍。同时，Eca 109 R50 Gy细胞中干细胞标志物β-连环蛋白水平升高。上述结果提示Eca 109 R50 Gy细胞具有肿瘤干细胞的某些特性。NS 398可增强Eca 109 R50 Gy细胞的放射敏感性，并下调β-catenin的表达。综上所述，放射抗性Eca 109 R50 Gy细胞具有CSC样细胞的特性，NS 398可增强CSC样Eca 109 R50 Gy细胞的放射敏感性，其作用可能部分通过下调β-catenin的表达。这些发现强调了CSCs在食管癌放射抵抗中的重要作用，并为考克斯-2抑制剂在CSCs中的可能应用提供了新的见解。
P>This study aimed to investigate the cancer stem cell (CSC) properties of radioresistant esophageal cancer cells and the radiosensitization effect of NS398, a cyclooxygenase (COX)-2 inhibitor, on them. Fractionated irradiation was applied to acquire radioresistant esophageal cancer cells. Clone formation assay was employed to detect cell radiosensitivity and cloning formation ability. Cell viability was determined by methyl tetrazolium colorimetry assay. Cell cycle distribution and apoptosis were detected by flow cytometry. Tumorigenicity was investigated by xenograft tumorigenicity assay. Expression levels of beta-catenin were detected by reverse transcription polymerase chain reaction or Western blot. As results, radioresistant Eca109R50Gy cells were obtained through fractional irradiation from Eca109 cells; Eca109R50Gy cells displayed higher ability of proliferation, colony-formation, and 40 times tumorigenic ability as high as that of the Eca109 cells in vivo. Meantime stem cell marker beta-catenin was elevated in Eca109R50Gy cells. All of the above implied that Eca109R50Gy cells have some properties of CSCs. NS398 enhanced the radiosensitivity of Eca109R50Gy cells accompanied by down-regulating the expression of beta-catenin. In conclusion, radioresistant Eca109R50Gy cells carried some CSC-like properties; NS398 enhanced the radiosensitivity of CSC-like Eca109R50Gy cells and this function may partly through down-regulating the expression of beta-catenin. These findings both stress the important role of CSCs in esophageal cancer radioresistance and provide new insight on possible application of COX-2 inhibitors on CSCs.