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.