吉非替尼按时辰给药对荷瘤裸鼠的药效学影响及机制研究-药理学专业论文.docxVIP

白的相对表达量表达在 4:00 和 8:00 明显降低（P0.05）；P-ERK1/2 蛋白表达在 4:00、 8:00、24:00 表达量明显降低（P0.05）。 4.与模型组相比，4:00、8:00 和 12:00 组肿瘤组织细胞凋亡率明显高于其他组。 结论： 吉非替尼对荷瘤裸鼠的移植瘤具有抑制作用，并且呈现出明显的时辰节律性的 差异，4:00，8:00 和 12:00 的抑制效果比 16:00，20:00 和 24:00 的好，其中 8:00 肿 瘤抑制效果最好，20:00 抑制效果最差，这种抑制作用产生的机制可能是通路抑制 EGFR/AKT/mTOR 和 EGFR/ERK 传导通路的信号传导有关。 关键词：吉非替尼；时辰药理学；药效学；作用机制 Abstract Objection: To investigate the antitumor effect of gefitinib at different dosing times and the underlying molecular mechanism via the PI3K/AKT/mTOR and MAPK/ERK pathway. Methods: we established a mice model of non-small cell lung cancer xenografts. The mice were randomly divided into six experimental groups and a model group and placed in alternating light and dark environments. After adaptive feeding for one week, the mice in the experimental groups were divided into six subgroups, which were given gefitinib orally at six different time points for 21 days. The mice in the model group were given the same amount of solvent. The changes of tumor volume were measured every three days. After the mice were sacrificed, the tumor tissue was removed and weighed to calculate the inhibition rate. The mRNA expression of EGFR, AKT and mTOR were assayed by quantitative real-time PCR. Protein expression levels of P-EGFR, P-AKT and P-mTOR were determined by Western blot analysis. Apoptosis of tumor tissue sections was detected by TUNEL. Results: Compared with the model group, the tumors in the experimental groups grew more slowly (P 0. 05, Figure 1), and the tumors grew more slowly in groups 8:00, 4:00 and 12:00 than in groups 16:00, 20:00 and 24:00. The tumor weight in all the experimental groups, except the 20:00 group, was significantly lower than that in the model group (P0. 05, Table2). The tumor weight in the groups 4:00，8:00, and 12:00 was significantly different from that in the 20:00 group (P0. 05). In all the experimental groups, the inhibition rate was the highest in the 8:00 group, and the lowest in the 20:00 group. The rel