多西紫杉醇在荷人鼻咽癌裸小鼠的时间化疗研究

目的观察多西紫杉醇时间给药对荷人鼻咽癌裸小鼠的疗效、不良反应，为多西紫杉醇在鼻咽癌时间化疗的临床应用提供理论依据。方法Balb/c裸小鼠，置于24 h程控光照调节的动物饲养柜中（12 h光照，12 h黑暗）同步化3周。接种人鼻咽癌细胞株（CNE2）于裸小鼠右侧腋部皮下，建立裸小鼠鼻咽癌移植瘤模型。70只荷瘤小鼠随机分为7组（6个给药组和1个对照组）,给药组荷瘤小鼠分别在3、7、11、15、19、23 HALO（hours after light onset，光照后时间）6个时间点给予腹腔注射多西紫杉醇（10 mg/kg），共3次。停药后第4天处死，计算各给药组抑瘤率，检测外周血白细胞(WBC)、血红蛋白(HB)和血小板(PLT)并观察体重变化。结果与对照组相比，多西紫杉醇对裸小鼠鼻咽癌移植瘤有明显的抑制作用（P=0.000）,抑瘤率在49%～83%。其中7HALO组抑瘤率最大，体重下降最少；23HALO组抑瘤率最小，体重下降最多（P<0.05）。各时间给药组裸小鼠外周血WBC、HB值与对照组相比均有下降，其中19、23HALO组WBC和HB值明显低于7、11HALO组（P<0.05）。结论多西紫杉醇对裸小鼠鼻咽癌移植瘤有明显的抑制作用。其中疗效及不良反应随不同时间给药而变化，7HALO最优，23HALO最差。

Chrono-chemotherapy of Docetaxel in Nude Mice Bearing Human Nasopharyngeal Carcinoma

Objective To observe the toxicity and efficacy of circadian injection of docetaxel on nude mice bearing human nasopharyngeal carcinoma.To provide the experimental data for the clinical use of docetaxel chronochemotherapy for therapy of nasopharyngeal carcinoma.Methods Balb/c nude mice synchronized 3 weeks in 24 h programmable light regulated animal feeding cabinet(12 hours light,12 hours dark).Nasopharyngeal carcinoma xenograft model was established by inoculating human nasopharyngeal carcinoma cell line(CNE2) into the right axilla of nude mice subcutaneously.Seventy tumor-bearing mice were randomly divided into 7 groups(6 treatment groups and 1 control group).Tumor-bearing mice in treatment groups were injected intraperitoneally with docetaxel at six time points:3,7,11,15,19,23 HALO(hours after light onset) respectively(10 mg/kg).Each mouse was injected 3 times.Mice were executed at 4th day after drug withdrawal.The tumor inhibition rate of each treatment group was calculated.White blood cell(WBC),hemoglobin(HB),platelet(PLT) values in peripheral blood were measured and the change of body weight were observed.Results Compared with the control group,nasopharyngeal carcinoma xenograft in nude mice was significantly inhibited after injection of docetaxel(P=0.000).The tumor inhibition rate ranged from 49% to 83%,with maximum in 7 HALO,minimum in 23 HALO.In contrast,weight loss was maximum in 23 HALO and minimum in 7 HALO(P<0.05).WBC and HB values in peripheral blood in each treatment group were both decreased,but that in 19,23 HALO group’s were significantly lower than that in 7,11 HALO group’s(P<0.05).Conclusion Docetaxel can significantly inhibit the nasopharyngeal carcinoma xenograft in nude mice.The efficacy and toxicity are different when drug is given at different circadian time.The optimal time of administration is at 7 HALO,while the worst is at 23 HALO.