cetuximab联合5-FU对直肠癌放射治疗敏感度影响的实验研究  

Effect of Cetuxiamb Combined with 5-fluorouracil on the Radiosensitivity of Colorectal Cancer Cells: An in vitro and in vivo Experimental Study

作　　者：左志贵[1] 王蓉蓉[2] 叶星照[1] 史壹雄[1] 姜有恒 宋华羽[1] 倪士昌[1] 蒋磊[3] Zuo Zhigui;Wang Rongrong;Ye Xingzhao(Department of Colorectal Surgery,The First Hospital of Wenzhou Medical University,Zhejiang 325000,China)

机构地区：[1]温州医科大学附属第一医院结直肠肛门外科,325000 [2]温州医科大学附属第一医院手术室,325000 [3]温州医科大学附属第一医院中心实验室,325000

出　　处：《医学研究杂志》2019年第2期66-70,共5页Journal of Medical Research

基　　金：浙江省自然科学基金资助项目(LY17H160056);浙江省医药卫生科技项目(2015KYA153);温州市科技局科研项目(Y20140372)

摘　　要：目的研究西妥昔单抗(cetuximab)联合氟尿嘧啶对结直肠癌细胞术前放射治疗效果的影响。方法对结肠癌细胞系RKO给予4种不同方式干预,2Gy放疗、氟尿嘧啶联合2Gy放疗、西妥昔单抗联合2Gy放疗、氟尿嘧啶及西妥昔单抗联合2Gy放疗,对各组细胞行CCK8检测不同干预后的细胞增殖情况,采用流式细胞术检测干预48h后各组细胞凋亡率、细胞周期比例,统计分析不同干预方式对RKO结直肠癌细胞系增殖的影响,利用RKO行裸鼠成瘤,对成瘤裸鼠同样给予4种不同方式干预并评估干预结果。结果西妥昔单抗及氟尿嘧啶各自单独联合放疗均提高了放射治疗对肿瘤细胞生长抑制作用,差异有统计学意义(P <0. 05),但氟尿嘧啶联合西妥昔单抗与各自单用比较对提高放射治疗效果不明显,抑制率比较差异无统计学意义(P>0. 05)。西妥昔单抗与2Gy放疗联合明显降低了G1/G0期肿瘤细胞的比例(P <0. 05),而氟尿嘧啶与2Gy放疗联合则导致细胞周期检测出现一个明显的凋亡峰。裸鼠成瘤实验显示2Gy+氟尿嘧啶组,2Gy+西妥昔单抗组瘤体重量均明显低于对照组,差异有统计学意义(P <0. 05),结果还显示2Gy+氟尿嘧啶组瘤体重量明显低于2Gy+西妥昔单抗组,差异有统计学意义(P <0. 05)。结论西妥昔单抗提高放疗敏感度主要通过改变细胞周期,减少引起对放疗损伤逃逸的G1/G0期细胞的比例,而氟尿嘧啶提高放疗敏感度主要通过增加细胞凋亡,氟尿嘧啶与西妥昔单抗比较增加放疗敏感度更加显著。氟尿嘧啶、西妥昔单抗各自单药均明显增加了2Gy放疗对裸鼠移植瘤的生长抑制作用,但西妥昔单抗联合氟尿嘧啶没有提高氟尿嘧啶单药对放疗敏感度的增加。Objective To assess whether cetuximab can enhance the preoperative combination effect of 5-fluorouracil and radiation in rectal cancer on basis of an in vitro and in vivo experimental study.Methods Human CRC cell lines RKO were irradiated with radiation(2Gy)alone,combing with 5-fluorouracil,cetuximab or both agents(5-fluorouracil and cetuximab).The cellular proliferation were evaluated by CCK8 assay.The cell apoptosis and cell-cycle distribution were investigated using FCM.The inhibitory effect on the growth of RKO xenogrsfts was assessed in athymic nude mice.Results CRC cell lines RKO treated with cetuximab and irradiated at 2Gy predominantly exhibited G 0/G 1 phase arrest in comparison with those in the control cells(P<0.05).In nude mice bearing RKO xenografts,one agent(5-fluorouracil or cetuximab)plus radiation significantly inhibited the tumor growth over radiation alone(P<0.05).Disappointing,the inhibitory rate of both agents(5-fluorouracil and cetuximab)plus radiation was not higher than that of 5-fluorouracil plus radiation(P>0.05),but the inhibitory rate of 5-fluorouracil alone plus radiation was significantly higher than that of cetuximab alone plus radiation(P<0.05).Conclusion 5-fluorouracil or cetuximab alone or both agents can enhance the radiosensitivity of rectal cancer,but 5-fluorouracil showed the better effect and cetuximab adding to 5-fluorouracil can not manifest the synergistic effect in experimental study.On the whole,it seems that the EGFR inhibitor cetuximab lacks the value of applying to the concurrent preoperative chemoradiation in locally advanced rectal cancer.

关 键 词：直肠癌 术前放疗 西妥昔单抗 氟尿嘧啶 

分 类 号：R735.3[医药卫生—肿瘤]