肿瘤坏死因子α通过丝裂原活化蛋白激酶激酶6诱导LA795肺腺癌细胞凋亡

The TNF-α-induced apoptosis of LA795 cells is mediated by MAP kinase kinase 6

目的 为了研究肿瘤坏死因子α(TNF α)诱导肺癌细胞凋亡的分子机制 ,寻找肺癌基因治疗的新方法。方法 建立TNF α诱导LA795肺腺癌细胞凋亡的细胞模型 ;使用人胚肾 2 93包装细胞制备丝裂原活化蛋白激酶激酶 6 (mitogen activatedproteinkinasekinase 6 ,MKK6 )及其结构活性和无活性突变体的重组腺病毒 ;使用激酶活性测定法检测细胞内MKK6的激酶活性。结果 TNF α刺激可明显诱导LA795肺腺癌细胞MKK6激活 ;用TNF α刺激肺腺癌细胞可明显诱导细胞凋亡 ;MKK6结构活性突变体也可明显诱导LA795细胞凋亡 ;而MKK6无活性突变体可明显抑制TNF α诱导的LA795细胞凋亡。结论 TNF α诱导LA795肺腺癌细胞凋亡是通过MKK6发挥作用的 。

Objective To study the molecular mechanism of apoptosis of lung cancer cells stimulated by tumor necrosis factor α for the discovery of potential methods of gene therapy of lung cancer. Methods The apoptosis model of LA795 adenocarcinoma cells was performed. Recombinant adenovirus of MAP kinase kinase 6, and its constitutively active form and dominant negative form were prepared in 293 package cells. Protein kinase assay was used to detect the activity of MKK6 in cells. Results TNF α stimulation increased the activity of MKK6 in LA795 lung cancer cells. The stimulation of TNF α induced apoptosis of LA795 cells significantly. The infection of recombinant virus of constitutive active form of MKK6 also induced apoptosis of LA795 cells significantly, while the infection of recombinant virus of dominant negative form of MKK6 blocked the apoptosis of LA795 cells apparently. Conclusions TNF α induced apoptosis of LA795 cells is mediated by MKK6. It is possible to use MKK6 recombinant virus for gene therapy of lung cancer.