荷瘤裸鼠按时辰给予吉非替尼的药效学研究

发布时间：2018-04-14 10:32

本文选题：吉非替尼 + 时辰药理学　；参考：《中国药房》2015年16期

【摘要】：目的:研究荷瘤裸鼠按时辰给予吉非替尼的药效学。方法:取BALB/c-nu裸鼠复制非小细胞肺癌模型后,随机分为不同时间给药的吉非替尼(4:00、8:00、12:00、16:00、20:00、24:00)组和模型组,每组10只。吉非替尼组裸鼠分别按相应时间ig给药1 mg/kg,模型组裸鼠ig给予等量的1%聚山梨酯80溶液,连续给药21 d。检测20 d内各组裸鼠的瘤体积及第21天时的瘤质量,计算抑瘤率;检测各组裸鼠肿瘤组织中表皮生长因子受体(EGFR)和细胞外调节蛋白激酶(ERK1/2)的m RNA及蛋白表达情况。结果:与模型组比较,各吉非替尼组裸鼠第18天时肿瘤体积均增加缓慢,除20:00组外其余各吉非替尼组裸鼠瘤质量降低、抑瘤率增加,其中4:00、8:00组裸鼠肿瘤组织中EGFR m RNA表达减弱,4:00、8:00、12:00组裸鼠肿瘤组织中ERK1/2 m RNA表达减弱,4:00、8:00、12:00、24:00组裸鼠肿瘤组织中p-EGFR蛋白表达减弱,4:00、8:00、24:00组裸鼠肿瘤组织中p-ERK1/2蛋白表达减弱,以上差异均具有统计学意义(P0.05)。与20:00组比较,4:00、8:00、12:00组裸鼠瘤质量降低,4:00、8:00组裸鼠肿瘤组织中p-EGFR蛋白表达减弱,8:00组裸鼠肿瘤组织中p-ERK1/2蛋白表达减弱,以上差异均具有统计学意义(P0.05)。结论:吉非替尼对荷瘤裸鼠具有瘤抑制作用,并呈现时辰节律性,其中8:00给药肿瘤抑制效果最好,20:00给药抑制效果最差;其机制可能与EGFR、ERK1/2介导的传导通路有关。
[Abstract]:Objective: to study the pharmacodynamics of gifitinib in tumor-bearing nude mice.Methods: BALB/c-nu nude mice were randomly divided into 4: 00: 8: 00 group and model group (10 rats in each group) of 4: 00: 8: 00 or 12: 00: 16: 00 20: 00: 24: 00) and the model group was divided into two groups: control group (n = 10) and model group (n = 10).The nude mice in gefitinib group were given 1 mg / kg ig at the corresponding time, and the model group were given the same amount of 1% polysorbate 80 solution intravenously for 21 days.The tumor volume and tumor mass of each group were measured within 20 days and the tumor inhibition rate was calculated. The expression of m RNA and protein in epidermal growth factor receptor (EGFR) and extracellular regulated protein kinase (ERK1 / 2) were detected.Results: compared with the model group, the tumor volume increased slowly in each gefitinib group on the 18th day, and the tumor mass decreased and the tumor inhibition rate increased in the other gefitinib groups except 20:00 group.The expression of EGFR m RNA in the tumor tissue of nude mice in 4: 00: 8: 00 group was weakened. The expression of ERK1/2 m RNA in the tumor tissue of nude mice in group 4: 00: 8: 00 and 12: 00: 00 was weakened. The expression of p-EGFR protein in tumor tissue of nude mice in group 4: 00: 8: 00: 2400 was weakened. The expression of p-ERK1/2 protein in tumor tissue of nude mice in group 4: 008: 00: 2400 was decreased.All the above differences were statistically significant (P 0.05).Compared with 20:00 group, the tumor quality of nude mice in 4: 00: 8: 12: 00 group was decreased. The expression of p-EGFR protein in tumor tissue of 4: 00 and 8: 00 group was decreased. The expression of p-ERK1/2 protein in tumor tissue of 8: 00 group was lower than that of 8: 00 group. The above differences were statistically significant (P 0.05).Conclusion: gefitinib has tumor inhibitory effect on tumor-bearing nude mice, and the inhibitory effect is the best at 8:00, and its mechanism may be related to the conduction pathway mediated by EGFRRERK1 / 2.
【作者单位】：青岛大学医学院;解放军第401医院药剂科;
【分类号】：R965

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