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α粒子体外照射致SAEC细胞恶性转化及肿瘤干细胞在转化细胞中的表达

发表时间:2011-06-15  浏览量:1367  下载量:631
全部作者: 张素萍,童建,Tom K HEI
作者单位: 苏州大学医学部放射医学与公共卫生学院;哥伦比亚大学医学院辐射研究中心
摘 要: 目的:建立α粒子体外照射致人肺小气道上皮细胞(small airway epithelial cells,SAEC)恶性转化的模型,检测肿瘤干细胞在恶性转化细胞中的表达。方法:α粒子不同剂量(0.2,0.4,0.8,1.0,2.0 Gy)分单次和多次(4次)照射人肺SAEC细胞,检测照射后不同阶段细胞的转化能力,包括血清抗性、增殖能力、磷乙酰-天冬氨酸[N-(phosphonoacetyl)-L-aspartate,PALA]抗性、软琼脂锚着独立生长能力、侵袭能力以及裸鼠成瘤能力。流式细胞仪检测转化细胞中肿瘤干细胞表面标记分子CD338和CD133的表达。检测免疫组化裸鼠成瘤组织中CD338和CD133的表达。结果:存活分数显示α粒子对SAEC细胞毒性呈现剂量-反应关系。转化早期细胞即对血清产生抗性,转化后期细胞对抗癌药物PALA产生抗性,细胞的增殖能力明显增强,在软琼脂中可锚着独立生长,侵袭能力也明显增强,其中0.8 Gy多次照射组细胞接种裸鼠形成肿瘤。流式细胞仪显示CD338和CD133表面分子在0.8 Gy组转化细胞中增多,免疫组化显示CD338和CD133在裸鼠成瘤组织中均呈阳性表达。结论:α粒子可致SAEC细胞发生恶性转化,肿瘤干细胞在转化细胞中明显增多。
关 键 词: 放射医学;辐射致癌;α粒子;小气道上皮细胞;恶性转化;肿瘤干细胞
Title: Malignant transformation of SAEC cells induced by α particle and expression of tumor stem cells in transformed cells
Author: ZHANG Suping, TONG Jian, Tom K HEI
Organization: School of Radiation Medicine and Public Health, Medical College of Soochow University; Center for Radiological Research, College of Physicians and Surgeons, Columbia University Medical Center
Abstract: Objective: To establish the malignant transformation model of small airway epithelial cells (SAEC) induced by α particle and detect the expression of tumor stem cells in transformed cells. Methods: SAEC cells were exposed to different doses (0.2, 0.4, 0.8, 1.0, 2.0 Gy) of α particles by single and multiple treatment. Survival fraction was detected using plating efficiency immediately after the irradiation. Cell transformation represented by resistance to serum and N-(phosphonoacetyl)-L-aspartate (PALA), cell proliferation, independent growth in soft agar, invasion ability and tumor growth in nude mice was measured. CD338 and CD133 were detected by flowcytometry and immunohistochemistry. Results: Survival fraction showed a dose-dependent manner of cytotoxicity of α particle on SAEC cells. Serum resistance and PALA resistance were observed in the process of transformation. All the cells in the irradiated groups could form colonies in soft agar, and with an increased invasion ability in the transformed cells. Three out of the five nude mice in the 0.8 Gy multiple treatment group formed tumors. CD338 and CD133 were increased in transformed SAEC cells and in tumor of nude mice. Conclusion: Human SAEC cells could be malignantly transformed in vitro by α particle and could form tumor in vivo in nude mice. Tumor stem cells increased in transformed cells.
Key words: radiation medicine; radiation carcinogen; α particle; small airway epithelial cells; malignant transformation; tumor stem cells
发表期数: 2011年6月第11期
引用格式: 张素萍,童建,Tom K HEI. α粒子体外照射致SAEC细胞恶性转化及肿瘤干细胞在转化细胞中的表达[J]. 中国科技论文在线精品论文,2011,4(11):1011-1020.
 
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