三氧化二砷对肺癌A549细胞及人脐静脉内皮细胞Notch通路的影响

Effects of arsenic trioxide on Notch pathway in A549 lung cancer cells and human umbilical vein endothelial cells

目的探索三氧化二砷（As2O3）对肺癌A549细胞和血管内皮细胞Notch通路相关分子表达的影响。方法体外培养人肺癌A549细胞和人脐静脉内皮细胞（HUVECs）,分别用0（空白对照）、0.5、1.0、2.0、4.0、8.0μmol·L-1的As2O3进行干预,24 h后收集细胞,定量PCR检测A549细胞Dll4 m RNA的水平、HUVECs Dll4和Notch-1 m RNA的水平。结果 A549细胞的Dll4 m RNA水平在0～2.0μmol·L-1组逐渐升高,2.0～8.0μmol·L-1组逐渐降低,且8.0μmol·L-1组的表达水平显著低于空白对照组（P〈0.01）;HUVECs的Dll4 m RNA水平在0～1.0μmol·L-1组逐渐升高,1.0～8.0μmol·L-1组逐渐降低,且4.0和8.0μmol·L-1组的表达水平显著低于空白对照组（P〈0.01）;HUVECs的Notch-1 m RNA水平随给药浓度的增加而升高,各浓度组均高于空白对照组（P〈0.01）。结论在体外条件下,As2O3在较低浓度能促进A549细胞和HUVECs Dll4 m RNA表达,而在较高浓度则抑制其表达;As2O3能浓度依赖性提高HUVECs的Notch-1 m RNA表达水平。

AIM To investigate the effects of arsenic trioxide（As2O3） on expression of molecules involved in Notch pathway in lung cancer cells and vascular endothelial cells.METHODS A549 human lung cancer cells and human umbilical vein endothelial cells（HUVECs） were cultured in vitro.Then,0,0.5,1.0,2.0,4.0and 8.0 μmol·L-1of As2O3 were added,and the cells were harvested after 24 h.RT-PCR was used to detect the Dll4 m RNA level in A549 cells,the Dll4 and Notch-1 m RNA levels in HUVECs.RESULTS The Dll4 m RNA level in A549 cells was risen in the 0-2.0 μmol·L-1groups,but was declined in the 2.0-8.0 μmol·L-1groups,and the level in the 8.0 μmol·L-1group was significantly lower than the blank control group（P 〈0.01）.The Dll4 m RNA level in HUVECs was risen in the 0-1.0 μmol·L-1groups,but was declined in the1.0-8.0 μmol·L-1groups,and the levels in the 4.0 and 8.0 μmol·L-1group was significantly lower than the blank control group（P 〈0.01）.The Notch-1 m RNA level in HUVECs was elevated with As2O3 in a dose-dependent manner,and the level in each As2O3 concentration group was significantly higher than the blank control group（P 〈0.01）.CONCLUSION In vitro,lower concentration of As2O3 could promote the expression of Dll4 m RNA in both A549 cells and HUVECs,while higher concentration of As2O3 could inhibit them.As2O3 could promote the expression of Notch-1 m RNA in HUVECs dose-dependently.