丙泊酚下调水通道蛋白3和基质金属蛋白酶-9表达抑制人肺癌A549细胞的侵袭力

Propofol suppresses invasion of human lung cancer A549 cells by down- regulating aquaporin-3 and matrix metalloproteinase-9

目的探讨丙泊酚对人肺癌A549细胞水通道蛋白3(AQP-3)、基质金属蛋白酶-9(MMP-9)表达及其侵袭力的影响。方法A549细胞经丙泊酚不同剂量(25、50、100μmol/L)和不同时间(12、24 h)处理。用RT-PCR方法观察丙泊酚对A549细胞AQP-3m RNA的作用,用Western Blot方法和Transwell侵袭实验分别检测不同浓度丙泊酚作用24 h对A549细胞AQP-3、MMP-9蛋白表达和细胞侵袭力的影响。结果与空白组比较,25、50、100μmol/L丙泊酚24 h处理组对AQP-3 m RNA表达的最大抑制比值为0.13,最小0.41;12 h处理组最大抑制比值0.19,最小0.65,差异有统计学意义(P<0.05);丙泊酚100μmol/L组24 h达到最大抑制效果(0.13±0.035)。25、50、100μmol/L丙泊酚24 h处理组AQP-3蛋白表达(0.91±0.009,0.60±0.020,0.57±0.006)和50、100μmol/L丙泊酚24 h处理组MMP-9蛋白表达(0.65±0.006,0.46±0.021),较空白组明显降低(P<0.05)。25、50、100μmol/L丙泊酚24 h处理组的穿膜细胞数(122.55±17.20,96.33±5.82,74.33±2.85),较空白组(199.33±23.88)明显减少(P<0.05)。结论丙泊酚50、100μmol/L处理24 h,可下调人肺癌A549细胞AQP-3 m RNA、AQP-3蛋白和MMP-9蛋白的表达,抑制A549细胞的侵袭力。

Objective To investigate the effect of propofol on cell invasion and expressions of aquaporin-3 （APQ-3） and matrix metalloproteinase-9 （MMP-9） in human lung adenocarcinoma cancer A549 cells. Method A549 cells were treated with propofol at the concentrations of 25, 50, and 100 μmol/L for 12 or 24 h. RT-PCR was used to detect the effect of propofol on AQP-3 mRNA level in A549 cells, and the effects of propofol treatments for 24 h on AQP-3 and MMP-9 protein expression and the invasive ability of A549 cells were assessed with Western blotting and Transwell assay, respectively. Results Compared with the control cells, the cells treated with 25, 50, and 100 μmol/L propofol showed a obvious inhibition of AQP-3 mRNA expression, with inhibition rates ranging from 0.19 to 0.65 in cells with a 12-h treatment and from 0.13 to 0.41 in cells treated for 24 h;100μmol/L propofol treatment for 24 h produced the strongest inhibitory effect （0.13 ± 0.035, P〈0.05）. AQP-3 protein expression in cells treated with 25, 50, and 100μmol/L propofol for 24 h （0.91 ± 0.009, 0.60 ± 0.020, and 0.57 ± 0.006, respectively） and MMP-9 protein expression in cells treated with 50 and 100 μmol/L propofol for 24 h （0.65 ± 0.006 and 0.46 ± 0.021, respectively） were significantly lower than those in the control cells （P〈0.05）. Treatment with 25, 50, and 100μmol/L propofol for 24 significantly lowered the number of invading cells （122.55 ± 17.20, 96.33 ± 5.82, and 74.33 ± 2.85, respectively） compared with the control group （199.33±23.88, P〈0.05）. Conclusion Treatment with 50 and 100μmol/L propofol inhibits cell invasion by down-regulating the expression of AQP-3 and MMP-9 in A549 cells.