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目的:探讨抑制表皮生长因子受体(EGFR)、胰岛素样生长因子1型受体(IGFR-1)活性对不同结肠癌细胞下游信号通路的影响及其产生的细胞生长抑制效应。方法:选择对EGFR抑制剂吉非替尼敏感性不同的结肠癌细胞,给予IGFR-1酪氨酸激酶抑制剂AG1024和吉非替尼单独或联合作用,以蛋白质印迹法检测EGFR、IGFR-1β及其下游信号蛋白AKT、MAPK表达和活性,以MTT法检测细胞增殖率。结果:LOVO细胞(吉非替尼敏感型)在吉非替尼作用下AKT、MAPK活性被抑制,P<0.05,而不论是否与AG1024联合;HT29细胞(吉非替尼中度敏感型)在吉非替尼和AG1024单独作用下AKT、MAPK活性均抑制不明显,而联合作用则其活性显著被抑制,P<0.05;HCT116细胞在AG1024作用下AKT、MAPK活性被抑制,P<0.05,而不论是否与吉非替尼联合。细胞增殖率显著降低见于吉非替尼作用下的LOVO细胞、吉非替尼联合AG1024作用下的HT29细胞以及AG1024作用下的HCT116细胞(P<0.05)。结论:吉非替尼联合AG1024可阻断下游信号通路的持续活化,在一定程度上可以改善结肠癌细胞对吉非替尼生长抑制作用的耐受。
AIM: To investigate the effects of inhibiting the activity of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGFR-1) on the downstream signaling pathways of different colon cancer cells and the cell growth inhibitory effect. METHODS: Colon cancer cells with different sensitivity to gefitinib as EGFR inhibitors were treated with AG1024, an inhibitor of IGFR-1 tyrosine kinase, and gefitinib alone or in combination. Western blotting was used to detect EGFR, IGFR-1β And its downstream signaling proteins AKT, MAPK expression and activity, MTT assay cell proliferation rate. RESULTS: Gefitinib sensitized LOVO cells to gefitinib treatment inhibited the activity of AKT and MAPK, P <0.05, regardless of whether they were combined with AG1024 or not. HT29 cells (moderate susceptibility to gefitinib) The activities of AKT and MAPK were not significantly inhibited by gefitinib and AG1024 alone, but their combined activities were significantly inhibited (P <0.05). The activity of AKT and MAPK in HCT116 cells was inhibited by AG1024 (P <0.05) Whether or not combined with gefitinib. Cell proliferation was significantly reduced in LOVO cells treated with gefitinib, HT29 cells treated with gefitinib and AG1024, and HCT116 cells treated with AG1024 (P <0.05). Conclusion: Gefitinib combined with AG1024 can block the sustained activation of the downstream signaling pathway, to a certain extent, colon cancer cells can improve the growth inhibition of gefitinib tolerance.