小剂量顺铂连续化疗对鼻咽癌CNE-1细胞放射敏感性影响的体外研究

摘要

Objective Using cell culture method to study about the effects of low-dose continuous cisplatin chemotherapy which simulated metronomic chemotherapy on the radiosensitivity in well-differentiated nasopharyngeal squamous cell carcinoma cell line CNE-1, and to provide a high efficiency and low toxicity of new treatment modalities to nasopharyngeal concomitant che-moradiotherapy in clinic. Methods MTT assay was used to evaluate the half inhibitory concentration (IC50, of cisplatin in nasopharyngeal carcinoma cell line CNE-1. The reference dose of low-dose chemotherapy was 1/5IC50, and IC70 as MTD reference dose. Cells of nasopharyngeal carcinoma were treated with cisplatin and radiation using four treatment protocols: 96h exposure to the dose of cisplatin l/SIC50 followed by irradiation( protocol A); 3h exposure to the dose of IC70 immediately after irradiation (protocol B) ; 3h exposure to IC70 followed by irradiation after a 93-h interval(protocol C) ; Cells which were not exposure to cisplatin cultured under the same conditions for 96h followed by irradiation( protocol D). The survival fraction were determined by the cell clonogenic survival assays, and survival curve were drawn by the single-hit multitarget model to compare the radiosensitivity of these treatment protocols. Results The IC^ of 72h exposure to cisplatin in nasopharyngeal carcinoma cell line CNE-1 was 0. 26 μg/ml , and the dose of 1/5IC50, and IC70 was 0. 05μg/ml and 0. 72μg/ml, respectively. The values of SF2 in protocols A , B , C and D calculated by the single-hit multitarget model was (0.414 ± 0. 008) , ( 0. 502 ± 0. 010) , ( 0. 411 ± 0.014) and (0.603 ± 0. 100) , respectively; and the SER in protocols A , B and C was (1.429 ± 0. 110) ,(1.012 ±0. 129)and( 1. 400 ± 0. 169), respectively. Conclusion The protocol of low-dose continuous cisplatin chemotherapy which simulated metronomic chemotherapy could increase radiation sensitivity of CNE-1.%目的 以小剂量顺铂连续化疗模拟节律化疗方式,采用细胞培养方法研究此种给药方式对鼻咽高分化鳞癌细胞株CNE-1细胞放射敏感性的影响,为临床鼻咽癌同步放化疗探索一种新的高效低毒的治疗模式.方法 MTT方法检测顺铂对鼻咽癌CNE-1细胞的半抑制浓度(IC50),1/5IC50为小剂量化疗参考剂量,而IC70则为MTD化疗参考剂量.细胞分4组进行如下处理:A组剂量为1/5IC50的顺铂连续作用96h后进行放疗；B组剂量为IC70的顺铂连续作用3h后立即给予放疗；C组为IC70作用3h后间隔93 h进行放疗；D组为未加入顺铂化疗的鼻咽癌细胞株同样条件下培养96h后进行放疗.克隆形成实验计算细胞存活率,采用单击多靶模型绘制剂量存活曲线,比较各处理组辐射敏感性变化.结果 顺铂对鼻咽癌CNE-1细胞株作用72h的IC50值为0.26μg/ml,1/5IC50为0.05μg/ml,IC70为0.72μg/ml.采用单击多靶模型计算各处理组的SF2值与SER值如下:A组SF2为(0.414±0.008),SER值为(1.429±0.110)；B组SF2值为(0.502±0.010),SER值为(1.012±0.129)；C组SF2值为(0.411±0.014),SER值为(1.400±0.169)；D组SF2为(0.603±0.100).结论 采用类似节律化疗方式给药,与放疗联用可以引起CNE-1细胞株放射敏感性增高.