厄洛替尼对肺癌模型小鼠的时辰药理学作用及相关机制研究  

Chronopharmacology of Erlotinib in Lung Cancer Model Mice and Its Mechanism

作　　者：王培培[1] 李明春[2] 刘姣[1] 张彬[1] 刘亮[1] 付青姐[2] 赵丽艳[2] 

机构地区：[1]青岛大学医学院药理学系,山东青岛266000 [2]解放军第401医院药剂科,山东青岛266071

出　　处：《中国药房》2014年第9期797-800,共4页China Pharmacy

摘　　要：目的:研究厄洛替尼按不同时辰给药的抗肿瘤作用,并探讨其可能的作用机制。方法:建立Levis肺癌细胞皮下移植瘤小鼠模型,随机分为A、B、C、D、E、F 6个厄洛替尼用药组和模型组,A^F组小鼠分别在对应的8:00、12:00、16:00、20:00、24:00、次日4:00灌胃给予厄洛替尼30 mg/kg,模型组小鼠给予同体积的羧甲基纤维素钠溶液。检测20 d内各组小鼠肿瘤体积及第21天时肿瘤瘤质量和肿瘤组织中表皮生长因子受体(EGFR)及其下游信号分子蛋白激酶B(PKB)、周期素依赖性激酶4(CDK-4)和细胞周期蛋白D1(Cyclin D1)mRNA的表达水平。结果:与模型组比较,A^F组小鼠肿瘤生长较缓慢(P<0.05),明期(8:00-16:00)肿瘤生长较暗期(20:00-次日4:00)缓慢,其中C组小鼠肿瘤生长最慢,E组小鼠肿瘤生长最快(P<0.05);A^F组小鼠瘤质量均降低,其中A、B、C组比D、E、F组降低明显,C组最明显;A、B、C组小鼠EGFR、PKB、Cyclin D1 mRNA表达较D、E、F组降低明显。结论:厄洛替尼对肺癌模型小鼠的抗肿瘤作用初步认为明期比暗期明显,其作用机制可能与EGFR/PKB/Cyclin D1/CDK-4介导的凋亡通路有关。OBJECTIVE： To study the antitumor effects of erlotinib with different dosing time and its underlying mechanism. METHODS： Levis lung cancer cell subcutaneously implanted tumor mice model was established, and then mice were randomly di- vided into erlotinib groups （A, B, C, D, E, F） and model group. Group A-F were given 30 mg/kg erlotinib intragastrically at 8： 00, 12： 00, 16： 00, 20 ： 00, 24： 00, 4： 00 of the next day. The model group received the same volume of Sodium carboxymethyl cel- lulose solution. The 20 d tumor volume and tumor weight on the 21th day of mice were measured. The mRNA expressions of EG- FR, PKB, CDK-4 and Cyclin D1 in tumor tissue were detected. RESULTS： Compared with model group, the tumor volume of mice decreased significantly in erlotinib group （P〈0.05） , more slowly in the light period （8： 00- 16： 00） than dark period （20： 00--4：00 of the next day）; the tumor growth of group C was the lowest while that of group E was the highest （P〈0.05）. The tumor weight decreased significantly in groups A-F, and the decsease of groups A, B and C were more significant than those of groups D, E and F and the antitumor effect of group C was best; mRNA expression of EGFR, PKB and Cyclin D1 decreased significantly in group A, B, C, D, compared with group D, E and F. CONCLUSIONS ： The antitumor effect of erlotinib on lung cancer mice is more significant in light period than in dark period. Its mechanism is partly related to EGFR-PKB-Cyclin D1-CDK-4 apoptosis pathway.

关 键 词：厄洛替尼 昼夜节律 时辰化疗 Levis肺癌细胞 抗肿瘤 机制 

分 类 号：R965[医药卫生—药理学]