胰腺癌细胞SW1990放疗抵抗性与其发生上皮间质转化的关系  

The relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of the Epithelial-Mesenchymal Transition： an in vitro study

作　　者：姜燕慧 游凯云[1] 毕卓菲[1] 李丽婷[1] 莫华倩 刘宜敏[1] Jiang Yanhui, You Kaiyun, Bi Zhuofei, Li Liting, Mo Huaqian, Liu Yimin(Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yatsen University, Guangzhou 510120, Chin)

机构地区：[1]中山大学孙逸仙纪念医院放疗科,广州510120

出　　处：《中华医学杂志》2018年第12期939-943,共5页National Medical Journal of China

基　　金：广东省自然科学基金（2016A030313361）

摘　　要：目的探讨胰腺癌细胞SW1990放疗抵抗性与其发生上皮间质转化（EMT）的关系。方法运用单次照射剂量逐渐递增的方法多次照射胰腺癌细胞SW1990，构建耐放疗胰腺癌细胞SW1990-R。倒置相差显微镜观察细胞形态，克隆形成试验检测细胞放疗抵抗性，流式细胞术检测4Gy照射后细胞凋亡情况。同时，采用Transwell实验检测细胞侵袭力，qRT—PCR检测EMT相关基因的表达情况，最后通过裸鼠移植瘤实验进一步验证SW1990放疗抵抗性与其发生EMT关系。结果与SW1990相比，SW1990-R放疗敏感性明显降低（SF2：0．3263±0．0073与0．8408±0．0019，P〈0．05）；经4Gyx线照射后，SW1990-R凋亡率较SW1990明显降低[（6．124-1．27）％与（16．87±1．73）％，P〈0．05]；Transwell结果示SW1990-R的侵袭能力较SW1990明显增强；并且在体内外实验中我们均发现：与SW1990相比，SW1990．R的Vimentin和Snail的表达水平明显升高，而E．cadhefin的表达水平明显降低，差异有统计学意义（P〈0．05）。结论与SW1990亲本细胞株相比，胰腺癌耐放疗细胞株SW1990-R可促进EMT的发生，其具体机制仍需进一步的研究。Objective To investigate the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of the Epithelial-Mesenchymal Transition （EMT）. Methods The radio-resistant pancreatic cancer cell SW1990-R were established by using the method of radiating pancreatic cancer cell SW1990 step by step and repeatedly. Then the changes of the morphology of the cell was observed by inverted phase contrast microscope, the radioresistance of SW1990-R was detected by colony- forming assay, and the apoptosis rate of the two cell lines after radiation were measured by flow cytometry. Then invasiveness and EMT-related genes was measured by trans-well test and qRT-PCR. Finally, the model of transplanted tumor on nude mouse was used to confirm the relationship between the radioresistance of pancreatic cancer cell SW1990 and the induction of EMT. Results Compared with SW1990, SW1990-R had a lower radiosensitivity （survival fraction in 2 Gy, SF2 ： 0. 326 3 ±0. 007 3 vs 0. 840 8±0. 001 9, P 〈 0.05） and lowerapoptosis rate[（6.12±1.27） % vs （16.87 ±1.73）%, P〈0.05]. Meanwhile, the invasive ability of SW1990-R were significant higher than that of SW1990 cell. According to the result of both in vivo and in vitro experiment, SW1990-R had a higher expression level of Vimentin and Snail, and lower expression level of E-cadherin when compared with SW1990. Conclusion Compared with SW1990, the radio-resistant pancreatic cancer cell SW1990-R can induce the Epithelial-mesenchymal transition.

关 键 词：胰腺肿瘤 放疗抵抗性 上皮间质转化 

分 类 号：R735.9[医药卫生—肿瘤]