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目的:观察CPT-11(艾力)时辰给药对鼻咽癌裸鼠的疗效、毒副反应以及细胞周期分布的变化,为CPT-11时辰化疗提供实验基础和临床应用参考。方法:统一光照条件下(光照时间7:00～19:00),黑暗时间(19:00～7:00)饲养3周、50只鼻咽癌移植瘤裸鼠模型分为给药组和对照组。给药组荷瘤小鼠在3、9、15、21HALO(Hours After Light Onset设光后小时)腹腔注射CPT-11 66mg/kg;15天后处死所有小鼠,检测各组小鼠的WBC、HB、PLT,然后剥离肿瘤计算各组抑瘤率,制成单个细胞悬液,固定,染色后流式细胞仪测DNA细胞周期含量;并取盲肠组织光镜下观察肠粘膜组织结构。结果:CPT-11对鼻咽癌移植瘤裸鼠有显著性疗效(P<0.01),其中15HALO,抑瘤率最大(P<0.05);而21HALO抑瘤率最小(P<0.05)。15HALO给药组WBC、HB、PLT数均高于其他各组(P<0.05),体重增加明显(P<0.05),光镜下粘膜损伤分级显著降低(P<0.05),21HALO给药组血象、体重增加最少,粘膜损伤分级较高(P<0.05)。9HALO要优于3HALO(P<0.05)。21HALO,3HALO细胞主要分布在G_2期(54.1100±17.3374053.0300±20.79316)。其中15HALO与21HALO差异最明显(P<0.01)。结论:CPT-11对鼻咽癌移植瘤裸鼠有明显的抑制作用且疗效及毒副作用呈现时辰节律变化(15HALO最优,21HALO最差),为CPT-11时辰化疗的临床应用提供了参考。
OBJECTIVE: To observe the curative effect, toxicity and change of cell cycle distribution of CPT-11 (AEI) on the nasopharyngeal carcinoma in nude mice and provide the experimental basis and clinical application reference for CPT-11. Methods: Under the condition of uniform illumination (light time 7: 00-19: 00) and dark time (19: 00-7: 00) for 3 weeks, 50 nude mice models of nasopharyngeal carcinoma xenografts were divided into the treatment group and the control group. The tumor-bearing mice in the administration group were intraperitoneally injected with CPT-11 66 mg / kg at 3, 9, 15, and 21 HALO (Hours After Light Onset); all mice were sacrificed 15 days later, and the WBC, HB , PLT, and then stripped of tumor inhibition rate of each group calculated to make a single cell suspension, fixed, stained flow cytometry measured DNA cell cycle content; and cecal tissue microscopic observation of intestinal mucosa tissue structure. Results: CPT-11 had a significant effect on nude mice bearing nasopharyngeal carcinoma (P <0.01), of which 15HALO had the highest inhibitory rate (P <0.05), while the inhibition rate of 21HALO was the lowest (P <0.05). The numbers of WBC, HB and PLT in 15HALO administration group were significantly higher than those in other groups (P <0.05), and the weight gain was significantly increased (P <0.05). The damage of mucosal injury was significantly reduced under light microscope (P <0.05) , Weight gain the least, higher mucosal injury classification (P <0.05). 9HALO was better than 3HALO (P <0.05). 21HALO, 3HALO cells were mainly distributed in G2 phase (54.1100 ± 17.3374053.0300 ± 20.79316). The difference between 15HALO and 21HALO was the most significant (P <0.01). CONCLUSION: CPT-11 has a significant inhibitory effect on nude mice with nasopharyngeal carcinoma xenografts. The curative effect and side-effect change of rhythms of CPT-11 (15HALO optimal, 21HALO worst) are numerically available for the clinical application of CPT-11.