肿瘤坏死因子相关诱导凋亡配体联合长春瑞滨联合干预诱导肺癌A549细胞凋亡及其机制

Mechanism of tumor necrosis factor related apoptosis inducing ligand and navelbine synergistically induced apoptosis in lung cancer A549 cells

目的探讨肿瘤坏死因子相关诱导凋亡配体（TRAIL）与长春瑞滨联合诱导肺癌细胞A549细胞凋亡可能的分子机制。方法利用噻唑蓝（MTT）及Western blot的方法，研究TRAIL对A549细胞增殖的抑制，以及其与死亡受体（DR）4、DR5、半胱氨酰天冬氨酸特异性蛋白酶（Caspase）-8、Caspase-3表达之间的关系。采用流式细胞术检测TRAIL联合长春瑞滨等肿瘤化疗药物对A549细胞凋亡的影响。结果TRAIL可以明显抑制肿瘤细胞A549的细胞增殖作用，提高A549细胞中DR5、Caspase-8、Caspase-3的蛋白表达水平，诱导细胞凋亡的发生。长春瑞滨在不同浓度的单药及与TRAIL联合给药的条件下，诱导的A549细胞的凋亡性分别为5．1600±0．5022、10．2600±0．4063、20．6100±1．4026；12．9200±1．0401、17．7700±0．8298、37．6700±2．0787。TRAIL联合长春瑞滨可以明显促进A549细胞的凋亡（P〈0．05）。结论TRAIL通过DR5、Caspase-8、Caspase-3信号通路诱导肺癌细胞A549发生凋亡。同时，TRAIL联合长春瑞滨可以明显提高A549细胞对药物敏感性，促进细胞凋亡的发生。

Objective To explore the potential molecular mechanism of tumor necrosis factor related apoptosis inducing ligand （TRAIL） and Navelbine （NVB） to induce apoptosis in lung cancer cell A549. Methods Methyl thiazol tetrazolium （MTT） was used to study the inhibition of TRAIL to A549 proliferation, and the relationship between TRAIL and the expression of death receptor （DR） 4, DR5, Caspase - 8, Caspase - 3. The using flow cytometry to detect the combined effects of TRAIL and NVB on A549 cell apoptosis. Results TRAIL could significantly inhibit the proliferation of tumor cells in A549 ceils, and the inhibition rate showed a positive dependence on the concentration of tumor cells. At the same time, TRAIL can significantly improve the expression level of Caspase - 8, Caspase - 3 and DR5 in A549 cells, and induce the apoptosis of cells. Vinorelbine at different concentrations of monotherapy and combined with TRAIL administration conditions induced apoptosis of A549 cells were 5. 160 0 ± 0. 502 2, 10.2600±0.4063, 20.6100± 1.4026; 12.9200± 1.0401, 17.7700± 0.8298, 37.6700± 2. 078 7. TRAIL combined with Changehun Red Sea could obviously promote the apoptosis of A549 cells, and it had statistical significance （ P 〈 0. 05 ）. Conclusion TRAIL can induce apoptosis in A549 via DR5, Caspase - 8 and Caspase - 3 this signal pathway. TRAIL also can combine with NVB to increase the sensitivity of A549, thus to accelerate the apoptosis of cells.