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(P<0.05)。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(P<0.05)。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。
OBJECTIVE： To study the pharmacodynamics of gefitinib in tumor-bearing nude mice according to time. METH- ODS： Non-small cell lung cancer models were replicated on BALB/c-nu nude mice and then randomly divided into gefitinib groups （4： 00, 8： 00, 12： 00, 16： 00, 20：00 and 24： 00） and model group, 10 for each. Nude mice in gefitinib groups were respectively given 1 mg/kg at the appropriate time for 21 d, ig; nude mice in model group were given the same volume of 1% tween-80 soln- tion for 21 d, ig. The ~mor volume within 20 d and the tumor weight in the 21st day were determined and the anti-tumor rate was calculated; the mRNA and protein expressions of epidermal growth factor receptor （EGFR） and extracellular regulated protein ki- nase （ERK1/2） in tumor tissue were determined. RESULTS： Compared with model group, the tumor volume of nude mice in gefi- tinib groups showed slower growth in the 18th day. Except for 20：00 group, the tumor weight of nude mice was decreased and an- ti-tumor rate was increased in all other gefitinib groups; among these, the mRNA expression of EGFR in tumor tissue in 4 ： 00 and 8 ： 00 groups was decreased, the mRNA expression of ERK1/2 in tumor tissue in 4： 00, 8： 00 and 12 ： 00 groups was decreased, the protein expression of p-EGFR in tumor tissue in 4： 00, 8：00, 12：00 and 24：00 groups was decreased and the protein expression of p-ERK1/2 in tumor tissue in 4： 00, 8：00 and 24：00 groups was decreased, all with significant differences （P〈0.05）. Compared with 20：00 group, the tumor weight in 4：00, 8：00 and 12：00 groups was decreased, the protein expression of p-EGFR in tumor tissue in 4：00 and 8：00 groups was decreased and the protein expression of p-ERK1/2 in tumor tissue in 8：00 group was de- creased, with significant differences （P〈0.05）. CONCLUSIONS： Gefitinib can inhibit the tumor of tumor-bearing nude mice with time rhythm. The best time of inhibitory effect is 8：00 and the worst is 20：00. The mechanism may be related to EGFR and ERK1/ 2 apoptosis pathway.
出处
《中国药房》
CAS
北大核心
2015年第16期2205-2208,共4页
China Pharmacy
关键词
吉非替尼
时辰药理学
药效学
作用机制
荷瘤裸鼠
Gefitinib
Chronopharmacology
Pharmacodynamics
Mechanism
Tumor-bearing nude mice
