干扰素λ对人肺腺癌细胞A549的增殖抑制作用及其机制研究

Effects and mechanism of IFNλ on human lung adenocarcinoma A549 cells

目的:探讨干扰素拉姆达(IFNλ)对人肺腺癌细胞A549的增殖抑制作用及其机制,为治疗肺癌提供理论依据。方法:本文以含有IL-10R1-IFNλR1(10R1-λR1)复合受体的质粒转染人肺腺癌细胞A549。以IL-10刺激转染细胞诱导IFNλ信号表达,在不同时间点进行细胞计数,用流式细胞术分析TUNEL染色、An-nexinV和PI细胞周期染色,以及活化STAT1的总量。结果:IFNλ对A549细胞增殖的抑制作用优于IFNα和IFNγ。表达10R1-λR1复合受体的A549细胞在IL-10刺激下IFNλ表达增加,TUNEL和AnnexinV染色阳性,PI染色显示细胞周期阻滞在G0/G1期。活化STAT1的表达总量增加,维持活性时间延长。结论:IFNλ信号可诱导人肺腺癌细胞凋亡,可能是通过激活STAT1蛋白实现的。

Objective：To investigate whether IFNλ could induce apoptosis in human lung cells, and provide theo- retic support for the anti - cancer and anti - viral applications of IFNλ. Methods ： Being great cell death after IFNλR1 overexpression, a chimeric receptor IL- 10R1 -IFNλR1 （10R1 -kR1 ） was used to transfect A549 lung cancer cells. Transfected cells were stimulated with IL - 10 to induce IFNλ signaling, and cell numbers were counted at dif- ferent time points. TUNEL assay, Annexin V staining and PI cell - cycle staining were conducted by using flow cy- tometry. The activated STAT1 protein levels were determined by flow cytometry. Results： IFNλ signaling inhibited A549 cell proliferation, better than IFNα or IFNλ. A549 cells expressing 10R1 - λR1 IL - 10 stimulation. TUNEL assay and Annexin V staining were both positive upon activated IFNλ signaling. The cell cycle was blocked at G0/G1 phase. The intensity and duration of activated STAT1 were stronger in A549 cells expressing 10R1 - λR1 stimulated by IL- 10 than in intact A549 cells stimulated by IFNλ. Conclusion： IFNλ signaling could induce apoptosis in lung carcinoma cell A549, which may via intensified and prolonged STAT1 activation.