本文關(guān)鍵詞： 厄洛替尼 時辰化療 晝夜節(jié)律 信號轉(zhuǎn)導(dǎo)途徑 表皮生長因子　出處：《中國藥理學(xué)與毒理學(xué)雜志》2015年02期 　論文類型：期刊論文

【摘要】：目的探討厄洛替尼按時辰給藥對肺癌裸鼠模型的抑瘤作用及其可能的作用機(jī)制。方法制備HCC827人肺癌細(xì)胞皮下移植瘤裸鼠模型,并隨機(jī)分為6個厄洛替尼組和模型組,每組10只。厄洛替尼組分別在08:00,12:00,16:00,20:00,24:00及次日04:00 ig給予厄洛替尼5 mg·kg-1,模型組給予與厄洛替尼組等體積分?jǐn)?shù)的溶劑磺丁基醚-β-環(huán)糊精溶液。測量21 d內(nèi)裸鼠腫瘤體積變化,處死裸鼠后剝離腫瘤并稱量其質(zhì)量,實(shí)時熒光定量PCR和Western蛋白印跡法檢測腫瘤組織中表皮生長因子受體(EGFR)及其下游信號轉(zhuǎn)導(dǎo)通路分子絲裂原激活蛋白激酶(MAPK)以及細(xì)胞周期蛋白依賴激酶抑制因子1A(P21Waf1)的m RNA和相關(guān)蛋白表達(dá)水平。結(jié)果與模型組比較,厄洛替尼08:00和次日04:00組腫瘤體積顯著縮小(P0.05);厄洛替尼08:00,12:00和次日04:00組腫瘤質(zhì)量顯著降低(P0.05)。與20:00組〔(0.70±0.36)g〕比較,08:00〔(0.30±0.17)g〕和次日04:00〔(0.39±0.29)g〕組裸鼠腫瘤質(zhì)量顯著降低(P0.05)。08:00組裸鼠腫瘤組織中EGFR和MAPK的m RNA表達(dá)水平顯著低于20:00組(P0.05),而P21Waf1 m RNA表達(dá)水平顯著高于模型組(P0.05)。厄洛替尼08:00和次日04:00組p-EGFR和p-MAPK蛋白表達(dá)顯著低于模型組(P0.05)。結(jié)論厄洛替尼時辰給藥對裸鼠移植肺癌的抗腫瘤作用具有時辰節(jié)律性,08:00給藥組效果最佳,其作用機(jī)制可能與EGFR/MAPK/P21Waf1信號轉(zhuǎn)導(dǎo)通路有關(guān)。
[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 鹵0.36 g). The tumor quality of the nude mice in the next day group (0430 鹵0.17g) and the next day (0430 鹵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.
【作者單位】： 青島大學(xué)醫(yī)學(xué)院藥理學(xué)系;解放軍第401醫(yī)院藥劑科;
【分類號】：R965

【共引文獻(xiàn)】

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