目录
摘要 II
关键字 II
ABSTRACT III
KEY WORDS III
引言 1
1 材料和方法 4
1.1 方案论证 4
1.2 材料 6
1.2.1 主要材料 6
1.2.2 主要仪器 6
1.3 方法 7
1.3.1 细胞培养和传代 7
1.3.2 细胞增殖和活力测定 7
1.3.3 Western blot检测EGFR、LC3表达 7
1.3.4 NSCLC裸鼠模型构建及给药预实验 8
1.3.5 统计学方法分析 8
2 结果与分析 9
2.1 ATO、EGFRTKIs及两药联合对NCIH1975细胞生长的影响 9
2.2 ATO、EGFRTKIs及两药联合对EGFR表达的影响 10
2.3 ATO、EGFRTKIs及两药联合处理后NCIH1975细胞的自噬情况 11
2.4 EGFRTKIs抑制NSCLC裸鼠模型的肿瘤生长情况 11
3 讨论与结论 12
致谢 15
参考文献 15
砷剂联合酪氨酸激酶抑制剂对非小细胞肺癌的治疗作用
摘要
目的：探究表皮生长因子受体酪氨酸激酶抑制剂（EGFRTKIs）与砷剂联合作用对非小细胞肺癌（NSCLC）耐药突变体细胞的生长抑制作用。方法：对NSCLC细胞NCIH1975进行细胞培养和传代，分别给予不同浓度的EGFRTKIs、砷剂及两药联合处理，用CCK8试剂分别检测其对细胞的生长抑制情况；用蛋白免疫印迹法检测细胞中EGFR及自噬标志物LC3的表达水平；构建裸鼠模型进行EGFRTKIs抑制肿瘤生长的预实验。结果：0.01、0.1、1、10 μM的EGFRTKIs，2、5 μM ATO及各浓度的两药联合均能抑制NCIH1975细胞的增殖，且两药联合对细胞的生长抑制作用强于两药单独作用；ATO及两药联合作用下调了EGFR蛋白表达；ATO、EGFRTKIs及两药联合均上调了LC3Ⅱ表达水平，且联合作用时更加显著；动物实验表明了EG *51今日免费论文网|www.51jrft.com +Q: ^351916072* 
FRTKIs能够抑制肿瘤生长。结论：ATO及EGFRTKIs均能抑制NCIH1975细胞的增殖，且当两者联合作用时，对细胞的生长抑制作用更强。
关键字：非小细胞肺癌；表皮生长因子酪氨酸激酶抑制剂；砷剂；两药联合
THE THERAPEUTIC EFFECTS OF COMBINING ARSENIC WITH EGFR TYROSINE KINASE INHIBITORS ON NONSMALL CELL LUNG CANCER
ABSTRACT
Objective: To investigate the cell growth inhibition of NSCLC resistant mutant when combining arsenic with RGFR tyrosine kinase inhibitor (EGFRTKI). Methods: The NSCLC cell line, NCIH1975, were cultured and treated with EGFRTKIs at different concentrations, arsenic trioxide, and a combination of two drugs. The viability of cells were measured using the Cell Counting Kit8 (CCK8) assay; The expression levels of EGFR and a biochemical marker of autophagy LC3 in cells were detected by Western blotting; Nude mouse model was established for EGFRTKIs preexperiment. Results: 0.01、0.1、1、10 μM EGFRTKIs, 2、5 μM arsenic trioxide (ATO) and the combination of two drugs can inhibit the proliferation of NCIH1975 cells, interestingly, when combining EGFRTKIs with ATO, the ability of cell growth inhibition is stronger than two drugs alone; ATO and the combination of two drugs downregulated EGFR protein expression; ATO、EGFRTKIs and the two combination all upregulated LC3Ⅱ expression levels and when the two worked together, the effect was more significant; animal experiment showed that EGFRTKIs inhibited tumor growth. Conclusion: Both ATO and EGFRTKIs can inhibit the proliferation of NCIH1975 cells, and when they are combined, the inhibitory effects on cells was stronger.

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