光卟啉介导的光动力治疗对胆管癌放疗增敏作用及机制  

Porphyrin mediated photodynamic therapy synergistically boosts the radiosensitivity of cholangiocarcinoma cells to ionizing radiation

作　　者：粟英[1] 王新星[1] 郭广成[1] 段馨[1] 窦东伟 常伟龙 Li Yiag;Wang Xinxing;Guo Guangcheng;Duan Xin;Dou Dongwei;Chang Weilong(Department of Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Chin)

机构地区：[1]郑州大学第一附属医院外科医学部,450052

出　　处：《中华实验外科杂志》2018年第7期1256-1258,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨光卟啉介导的低强度光动力治疗（PDT）增强胆管癌放疗作用及其机制。方法2’，7’-二氯荧光黄双乙酸（DCFH-DA）检测细胞内活性氧产量；细胞计数试剂盒（CCK-8）法检测单纯放疗、光敏剂＋放疗、PDT＋放疗后细胞活性；流氏细胞术检测细胞凋亡；平板克隆检测肿瘤细胞克隆抑制；Western blot检测相关蛋白表达。结果低强度PDT可提高肿瘤细胞内活性氧负荷并显著增强放疗对胆管癌细胞的增殖抑制和促凋亡作用，PDT＋放疗组和单纯放疗组的凋亡率分别为（15．45±1．23）％和（6．35±0．84）％（P=0．001）；PDT的放疗增敏率（SER10）为1．59，优于顺铂和紫杉醇的1．27和1．32；PDT的放疗增敏效果优于常用增敏剂紫杉醇和顺铂；PDT联合放疗组磷酸化细胞外调节蛋白激酶（p-ERK）和磷酸化蛋白激酶B（p-Akt）表达量较单纯放疗组减少，分别下降了（53．6±14．2）％（P=0．017）和（49．8±17．5）％（P=0．023），同时凋亡相关蛋白B淋巴细胞瘤。2（bcl-2）表达减少[（36．8±9．8）％，P=0．027]，bcl-2相关X蛋白（bax）增加[（51．3±18．4）％，P=0．012]。结论低强度PDT能显著提高胆管癌的放疗敏感性。Objective To explore the effect of low intensity of porphyrin mediated photodynamic therapy （PDT） on the radiosensitization in cholangiocarcinoma cells and its related mechanisms. Methods 2, 7 -Dichlorodi -hydrofluorescein diacetate （DCFH -DA） probe was used to detect the intracellular reactive oxygen species （ROS） production; Cell viability was evaluated by cell counting kit -8 （CCK -8 ） assays. Flow cytometry was used to quantify the apoptotic level of cells; Clonogenic survival assay was performed to assess the radiosensitizing effect of the radiosensitizer; Apoptosis related proteins were detected by Western blotting. Results Low intensity of PDT does not lead to death of QBC939 ceils, whereas provides an elevated ROS environment in the mitochondria. The increasing intracellular level of ROS is demonstrated to enhance the radiosensitivity of QBC939 ceils with a supra - additive synergistic effect of ＂0 ＋ 1 〉 1 ＂. The apoptotic rates in the PDT ＋ radiotherapy group and the radiotherapy alone group were （15.45 ± 1.23）% and （6. 35 ± 0. 84）% respectively （P =0. 001 ）. In addition, the low intensity of PDT achieves a high SER10 value of 1.59, which is much larger than that of the most popularly used radiosensitizers, cisplatin （ 1.27 ）, and paclitaxel （1.32）. The expression of phosphorylated RAC - alpha serine/threonine - protein kinase （ p - Akt） and phosphorylated extracellular regulated protein kinases （ p - ERK） proteins decreased more significant after PDT ＋ radiotherapy when compared to the radiotherapy alone （ p - AKT and p - ERK were declined by （53.6 ± 14. 2） % and （49. 8 ± 17. 5 ） %, respectively）. Conclusion Low intensity of PDT is an ideal method for radiotherapy sensitization and has great potential for clinical application.

关 键 词：胆管癌 光动力治疗 放疗增敏 细胞凋亡 

分 类 号：R735.1[医药卫生—肿瘤]