厄洛替尼时辰给药对肺癌模型裸鼠的抑瘤作用及作用机制

发布时间：2018-02-08 19:40

本文关键词： 厄洛替尼时辰化疗昼夜节律信号转导途径表皮生长因子　出处：《中国药理学与毒理学杂志》2015年02期 　论文类型：期刊论文

【摘要】：目的探讨厄洛替尼按时辰给药对肺癌裸鼠模型的抑瘤作用及其可能的作用机制。方法制备HCC827人肺癌细胞皮下移植瘤裸鼠模型,并随机分为6个厄洛替尼组和模型组,每组10只。厄洛替尼组分别在08:00,12:00,16:00,20:00,24:00及次日04:00 ig给予厄洛替尼5 mg·kg-1,模型组给予与厄洛替尼组等体积分数的溶剂磺丁基醚-β-环糊精溶液。测量21 d内裸鼠肿瘤体积变化,处死裸鼠后剥离肿瘤并称量其质量,实时荧光定量PCR和Western蛋白印迹法检测肿瘤组织中表皮生长因子受体(EGFR)及其下游信号转导通路分子丝裂原激活蛋白激酶(MAPK)以及细胞周期蛋白依赖激酶抑制因子1A(P21Waf1)的m RNA和相关蛋白表达水平。结果与模型组比较,厄洛替尼08:00和次日04:00组肿瘤体积显著缩小(P0.05);厄洛替尼08:00,12:00和次日04:00组肿瘤质量显著降低(P0.05)。与20:00组〔(0.70±0.36)g〕比较,08:00〔(0.30±0.17)g〕和次日04:00〔(0.39±0.29)g〕组裸鼠肿瘤质量显著降低(P0.05)。08:00组裸鼠肿瘤组织中EGFR和MAPK的m RNA表达水平显著低于20:00组(P0.05),而P21Waf1 m RNA表达水平显著高于模型组(P0.05)。厄洛替尼08:00和次日04:00组p-EGFR和p-MAPK蛋白表达显著低于模型组(P0.05)。结论厄洛替尼时辰给药对裸鼠移植肺癌的抗肿瘤作用具有时辰节律性,08:00给药组效果最佳,其作用机制可能与EGFR/MAPK/P21Waf1信号转导通路有关。
[Abstract]:Objective to investigate the inhibitory effect of erlotinib on lung cancer in nude mice and its possible mechanism. Methods HCC827 human lung cancer cells were subcutaneously transplanted into nude mice, and were randomly divided into 6 groups and 6 groups. 10 rats in each group were given erlotinib 5 mg 路kg -1 by ig at 0 8: 00 12: 00 16: 00 20: 00 at 24: 00, and the model group were given the same volume fraction of solvent Ding Ji-尾 -cyclodextrin solution as erlotinib group at 04:00 the next day. The tumor volume of nude mice was measured within 21 days. After the nude mice were killed, the tumor was stripped and weighed. Detection of epidermal growth factor receptor (EGFR) and its downstream signal transduction pathway, mitogen-activated protein kinase (MAPK), and cyclin dependent kinase inhibitor 1Ap21Waf1 by real-time quantitative PCR and Western Western blotting. The expression levels of m RNA and related proteins were compared with those of the model group. The tumor volume in the 08:00 and 04:00 groups decreased significantly (P 0.05), and the tumor quality in the group of erlotinib 08: 00: 00 and 04:00 decreased significantly compared with the group 04:00 (0.70 卤0.36 g). The tumor quality of the nude mice in the next day group (0430 卤0.17g) and the next day (0430 卤0.29 g) significantly decreased the EGFR in the tumor tissue of the nude mice. The expression level of m RNA and MAPK was significantly lower than that of 20:00 group, while the expression level of P21Waf1 m RNA was significantly higher than that of model group P0.05.The expression of p-EGFR and p-MAPK protein in erlotinib 08:00 and 04:00 group was significantly lower than that in model group P0.05.Conclusion the expression of erlotinib in nude mice is significantly lower than that in the model group. The antitumor effect of transplanted lung cancer was the best in the treatment group of 08: 00. The mechanism may be related to EGFR/MAPK/P21Waf1 signal transduction pathway.
【作者单位】：青岛大学医学院药理学系;解放军第401医院药剂科;
【分类号】：R965

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