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目的研究舒尼替尼与吉西他滨单药、联合及序贯应用对人肺腺癌A549细胞增殖及凋亡的作用及其机制。方法实验分为对照组、舒尼替尼组、吉西他滨组、舒尼替尼序贯吉西他滨组、吉西他滨序贯舒尼替尼组和联合组。A549细胞经舒尼替尼与吉西他滨单药、联合及序贯作用后,MTT法检测细胞增殖;Hoechst 33258染色法检测细胞凋亡形态;流式细胞术检测细胞凋亡及周期分布;Western blotting检测磷酸化细胞外调节蛋白激酶(P-ERK1/2)及磷酸化蛋白激酶B(P-AKT)的表达。结果 A549细胞对舒尼替尼耐药,对吉西他滨敏感。与吉西他滨组相比,吉西他滨序贯舒尼替尼组A549细胞增殖抑制率及凋亡率明显增高(P<0.05)。舒尼替尼与吉西他滨分别阻滞A549细胞于G1期及S期。与对照组相比,舒尼替尼序贯吉西他滨组G1期细胞增多(P<0.05),S期细胞减少(P<0.05)。与舒尼替尼组相比,吉西他滨序贯舒尼替尼组A549细胞P-ERK1/2与P-AKT的表达降低(P<0.05)。结论吉西他滨序贯舒尼替尼作用于A549细胞具有协同作用,其机制与酪氨酸激酶受体信号通路的表达有关。
Objective To study the effect of sunitinib and gemcitabine on the proliferation and apoptosis of human lung adenocarcinoma A549 cells induced by monotherapy, combination and sequential therapy. Methods The experiment was divided into the control group, the sunitinib group, the gemcitabine group, the sunitinib sequential gemcitabine group, the gemcitabine sequential sunitinib group and the combination group. A549 cells were treated with sunitinib and gemcitabine alone, in combination and sequential manner, cell proliferation was detected by MTT assay; apoptosis morphology was detected by Hoechst 33258 staining; apoptosis and cycle distribution were detected by flow cytometry; Western blotting Phosphorylation of extracellular regulated protein kinase (P-ERK1 / 2) and phosphorylated protein kinase B (P-AKT) expression. Results A549 cells were resistant to sunitinib and sensitive to gemcitabine. Compared with gemcitabine group, the inhibitory rate and apoptosis rate of A549 cells in gemcitabine sequential sunitinib group were significantly increased (P <0.05). Sunitinib and gemcitabine blocked A549 cells in G1 phase and S phase, respectively. Compared with the control group, the cells in G1 phase of sunitinib sequential gemcitabine group increased (P <0.05) and S phase cells decreased (P <0.05). Compared with the sunitinib group, the expression of P-ERK1 / 2 and P-AKT in gemcitabine-treated sunitinib group A549 cells decreased (P <0.05). Conclusion Gemcitabine sequential sunitinib has a synergistic effect on A549 cells, and its mechanism is related to the expression of tyrosine kinase receptor signaling pathway.