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目的探讨阿司匹林对人胰腺癌细胞上皮间质转化(EMT)和吉西他滨耐药性的影响。方法应用MTT法检测阿司匹林(0、1、2、5、10mmol/L)对三种胰腺癌细胞(SW1990、PATU-8988、PANC-1)生存率的影响以及阿司匹林(2mmol/L)与吉西他滨(0.05mg/L)联合用药对SW1990细胞增殖的影响。平板克隆实验检测药物对克隆形成能力的影响;流式细胞术检测细胞凋亡情况;细胞划痕实验观察细胞的迁移能力;Western blot检测凋亡相关蛋白及EMT相关蛋白表达水平。结果(1)与对照组相比,低浓度阿司匹林(1、2mmol/L)对PATU-8988、PANC-1有生长抑制作用(P<0.05、P<0.01);高浓度阿司匹林(5、10mmol/L)对SW1990、PATU-8988、PANC-1均有较明显的生长抑制作用(P<0.05、P<0.01)。(2)与单药组相比,联合用药组中SW1990细胞增殖率显著降低,克隆形成率显著降低,凋亡率显著升高(P<0.05),细胞中的Bcl-2蛋白表达水平显著降低。(3)与单药组相比,联合用药组细胞迁移率显著降低,细胞中的EMT相关蛋白E-钙黏蛋白表达显著升高,波形蛋白表达显著降低。结论阿司匹林有抑制胰腺癌细胞增殖的作用,并且能增强细胞对吉西他滨的敏感性,同时逆转胰腺癌细胞EMT。
Objective To investigate the effect of aspirin on the proliferation of human pancreatic cancer cells in epithelial-mesenchymal transition (EMT) and gemcitabine resistance. Methods The effects of aspirin (0, 1, 2, 5, 10mmol / L) on the survival rates of three kinds of pancreatic cancer cells (SW1990, PATU-8988 and PANC-1) were detected by MTT assay. The effects of aspirin (2mmol / L) and gemcitabine 0.05mg / L) on the proliferation of SW1990 cells. The effect of the drug on the clonality was detected by plate clone assay. The apoptosis was detected by flow cytometry. The cell migration was observed by cell scratch assay. The expression of apoptosis-related protein and EMT-related protein were detected by Western blot. Results Compared with the control group, the low concentration aspirin (1,2 mmol / L) had the inhibitory effect on PATU-8988 and PANC-1 (P <0.05, P <0.01) L) had obvious growth inhibitory effect on SW1990, PATU-8988 and PANC-1 (P <0.05, P <0.01). (2) Compared with single drug group, the proliferation rate of SW1990 cells in combination group was significantly decreased, the colony formation rate was significantly decreased, the apoptosis rate was significantly increased (P <0.05), and the expression of Bcl-2 protein was significantly decreased . (3) Compared with the single drug group, the cell migration rate of the combination group was significantly decreased, the EMT-related protein E-cadherin expression was significantly increased, the vimentin expression was significantly reduced. Conclusions Aspirin can inhibit the proliferation of pancreatic cancer cells and enhance the sensitivity of cells to gemcitabine and reverse the EMT of pancreatic cancer cells.