埃索美拉唑抑制胃癌AGS细胞增殖与蛋白激酶B、表皮生长因子受体表达的关系

Relationship between the proliferation inhibition of AGS cells treated with esomeprazole and the expression of protein kinase B and epidermal growth factor receptor

目的探讨埃索美拉唑对人胃癌AGS细胞增殖、迁移、凋亡的影响及其与蛋白激酶B（Akt）、表皮生长因子受体（EGFR）表达的关系。方法分别用噻唑蓝（MTT）法和Transwell实验分析不同浓度的埃索美拉唑（0、2.5、5.0、10.0、20.0、40.0、80.0 mg/L）对胃癌AGS细胞增殖、迁移、侵袭的影响；用流式细胞术检测埃索美拉唑（40 mg/L）作用胃癌AGS细胞48 h后其细胞凋亡；分别用反转录-聚合酶链反应（RT-PCR）和Western blot方法检测埃索美拉唑（40 mg/L）作用胃癌AGS细胞48 h后Akt、EGFR、半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-3、Caspase-7 mRNA和蛋白的表达。结果随着埃索美拉唑浓度的增加，胃癌AGS细胞抑制率逐渐增加（0.00、9.76%、9.97%、13.13%、24.54%、43.62%、55.59%，P＝0.001），迁移细胞数逐渐减少[（247.38±7.31）、（240.35±4.30）、（225.89±7.36）、（210.27±4.16）、（181.38±6.23）、（142.46±4.13）、（122.48±6.25）个/视野，P＝0.001]，侵袭细胞数逐渐减少[（207.32±13.23）、（201.34±9.43）、（197.49±5.98）、（189.74±11.65）、（172.18±7.38）、（150.49±6.39）、（111.23±6.36）个/视野，P＝0.001]。埃索美拉唑40 mg/L处理48 h后，细胞凋亡比例显著增加（30.50%比2.88%），Akt、Caspase-3、Caspase-7 mRNA和蛋白表达下降，EGFR mRNA和蛋白表达升高。结论埃索美拉唑能抑制胃癌AGS细胞增殖，诱导其凋亡，可能与Akt表达下降、EGFR的激活有关。

Objective To investigate the effect of esomeprazole on proliferation, migration, apoptosis of gastric cancer cell line AGS cells and its relationship with protein kinase B （Akt）, epidermal growth factor receptor （EGFR） expression.Methods Methyl thiazol tetrazolium （MTT） method and Transwell model analysis were used to detect proliferation, migration and invasion ability of AGS cells treated with different concentrations of esomeprazole （0, 2.5, 5.0, 10.0, 20.0, 40.0, 80.0 mg/L）. Flow cytometry was used to examine apoptosis of AGS cells treated with esomeprazole （40 mg/L） after 48 h. Reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting were used to detect the Akt, EGFR, cysteinyl aspartate-specific protease （Caspase）-3, Caspase-7 mRNA and protein expression in AGS cells treated with esomeprazole （40 mg/L） after 48 h.Results Inhibition rate of AGS cells was increased （0.00, 9.76%, 9.97%, 13.13%, 24.54%, 43.62%, 55.59%, P=0.001） with the increase of esomeprazole concentration, while the number of migrating cells gradually declined [（247.38±7.31）, （240.35±4.30）, （225.89±7.36）, （210.27±4.16）, （181.38±6.23）, （142.46±4.13）, （122.48±6.25） cells per microscopic vision, P=0.001] and also that of invading cells [（207.32±13.23）, （201.34±9.43）, （197.49±5.98）, （189.74±11.65）, （172.18±7.38）, （150.49±6.39）, （111.23±6.36） cells per microscopic vision, P=0.001]. The apoptosis rate of AGS cells was increased significantly （30.50% vs. 2.88%） after treatment with esomeprazole （40 mg/L） for 48 h, Akt, Caspase-3 and Caspase-7 mRNA and protein expression decreased, but EGFR mRNA and protein expression increased.Conclusion Esomeprazole could inhibit AGS cells proliferation and induce the apoptosis, with a possible mechanism of Akt downregulation and EGFR activation.