异丙酚通过Wnt/β-catenin信号通路对肺癌的调控机制分析

Analysis of the regulatory mechanism of propofol on lung cancer through Wnt/β-catenin signaling pathway

目的 分析异丙酚通过Wnt/β-catenin信号通路对肺癌的调控机制。方法 分别采用浓度为0、2.5、5.0、10.0、20.0μmol/L的异丙酚对H460肺癌细胞进行72 h处理,并于培养24、48、72 h时检测各组细胞的增殖、凋亡、迁移、侵袭情况,并比较各组细胞培养72 h后的增殖细胞核抗原(PCNA)、Bcl-2相关X蛋白(Bax)、基质金属蛋白酶(MMP)-2、MMP-9、Wnt1、β-连环蛋白(β-catenin)蛋白表达水平。结果 使用不同浓度异丙酚对H460肺癌细胞处理24、48、72 h后,随着处理时间的延长各组细胞的吸光度值均升高,培养24、48、72 h时,2.5μmol/L组、5.0μmol/L组、10.0μmol/L组、20.0μmol/L组的细胞吸光度值均低于0μmol/L组,且2.5μmol/L组最高,20.0μmol/L组最低,呈剂量反应;随着处理时间的延长各组细胞迁移、侵袭个数均增多,培养24、48、72 h时,2.5μmol/L组、5.0μmol/L组、10.0μmol/L组、20.0μmol/L组的细胞迁移、侵袭个数均少于0μmol/L组,且2.5μmol/L组最多,20.0μmol/L组最少,呈剂量反应;随着处理时间的延长各组细胞凋亡率均升高,培养24、48、72 h时,2.5μmol/L组、5.0μmol/L组、10.0μmol/L组、20.0μmol/L组的细胞凋亡率均高于0μmol/L组,且2.5μmol/L组最低,20.0μmol/L组最高,呈剂量反应。使用不同浓度异丙酚对H460肺癌细胞处理72 h后,2.5μmol/L组、5.0μmol/L组、10.0μmol/L组、20.0μmol/L组的PCNA、MMP-2、MMP-9、Wnt1、β-catenin蛋白表达水平均低于0μmol/L组,且2.5μmol/L组最高,20.0μmol/L组最低;2.5μmol/L组、5.0μmol/L组、10.0μmol/L组、20.0μmol/L组的Bax蛋白表达水平均高于0μmol/L组,且2.5μmol/L组最低,20.0μmol/L组最高,呈现剂量反应。结论 异丙酚可通过抑制Wnt/β-catenin信号通路抑制H460肺癌细胞增殖、迁移、侵袭,促进细胞凋亡,且作用效果随异丙酚剂量的升高而显著。

Objective To analyze the regulatory mechanism of propofol on lung cancer through Wnt/β-catenin signaling pathway. Methods The concentrations of 0, 2.5, 5.0 and 10.0 μmol/L were used respectively. H460 lung cancer cells were treated with propofol at 20.0 μmol/L for 72 h, and the proliferation, apoptosis, migration and invasion of cells in each group were detected at 24, 48 and 72 h of culture, and the comparison of each group was made. The levels of PCNA, Bax, MMP-2, MMP-9,Wnt1, β-catenin protein expression after 72 h of cell culture. Results After H460 lung cancer cells were treated with different concentrations of propofol for 24, 48 and 72 h, the A value of cells in each group increased with the prolongation of treatment time. The absorbance values of cells in the 2.5 μmol/L group, 5.0 μmol/L group, 10.0 μmol/L group, and 20.0 μmol/L group were all lower than those in the 0 μmol/L group, with the highest in the 2.5 μmol/L group and the lowest in the 20.0 μmol/L group, showing a dose-response. The number of cells migrating and invasive in each group increased during the prolongation period. At 24, 48 and 72 h, the number of cells migrating and invasive in the 2.5 μmol/L group, 5.0 μmol/L group, 10.0 μmol/L group and 20.0 μmol/L group all were less than the 0 μmol/L group, and the 2.5 μmol/L group was the most, and the 20.0 μmol/L group was the least, showing a dose response;with the prolongation of the treatment time, the apoptosis rate of each group increased, the apoptosis rate of 2.5 μmol/L group, 5.0 μmol/L group, 10.0 μmol/L group and 20.0 μmol/L group were all higher than 0 μmol/L group, and the 2.5 μmol/L group was the lowest, and the 20.0 μmol/L group was the lowest. the highest, showing a dose-response. After treating H460 lung cancer cells with different concentrations of propofol for 72 h, the levels of PCNA, MMP-2, MMP-9, Wnt1, β-catenin protein expression were lower than those of the 0 μmol/L group, the highest in the 2.5μmol/L group and the lowest in the 20.0 μmol/L group. The level of Bax protein expression in 2.5 μmol/L group was the lowest, and the 20.0 μmol/L group was the highest, showing a dose-response. Conclusion Propofol can inhibit the proliferation, migration and invasion of H460 lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway, and promote cell apoptosis, and the effect is significant with the increase of propofol dose.