中文摘要：

目的研究IFN_α对人皮肤T细胞淋巴瘤（CTCL）细胞的增殖抑制和凋亡诱导作用，探讨IFN_α治疗CTCL的机制。方法分别用3000，5000，10000，20000U／mL的IFN_α作用Hut78细胞24，48，72h后，利用MTS法检测Hut78细胞的生存率；并用流式细胞术检测不同浓度IFN_α仅作用细胞24h后，Hut78细胞的凋亡情况。运用ReaL-time PCR检测不同时间点IFN_α作用后，BCL11B mRNA的表达情况，Westem blot检测不同时间点IFN_α作用后BCL11B蛋白的表达情况，免疫荧光检测IFN_α不同时间点作用后，BCLllB蛋白在Hut78细胞表达程度和分布情况。结果IFN_α能明显抑制Hut78细胞的增殖，且这种作用呈剂量依赖性和时间依赖性。其抑制效应在48h达到峰值。IFN_α还能显著诱导Hut78细胞的凋亡，其作用亦呈浓度依赖性。10000U／mL IFN_α作用细胞3，6，9，12h后，BCLllB mR-NA表达均显著降低，其中在6h时间点BCLllB的mRNA表达下降到最低点，10000U／mL IFN_α作用细胞6，12，24h后BCLllB的蛋白也明显降低，在12h时间点，BCLllB的蛋白表达量下降至最低。结论IFN_α通过抑制细胞增殖和促进细胞凋亡对CTCL起到治疗作用，并可通过降低BCLllB的表达，促进细胞凋亡．并提高CTCL细胞对常规化疗的敏感性。

英文摘要：

Objective To study the effects of IFN_α on the proliferation and apoptosis of human cutaneous T cell lymphoma modeled cell line Hut-78, and to explore the molecular mechanism underlying it. Methods Hut78 cells were incubated with 3 000U ,5 000U, 10 000U ,20 000U/ml IFN_α for 24, 48, 72 hours. Cell viability assays were performed to measure MTS-based cell viability at each time points. Cell apoptosis after IFN_α incubation was quantified by flow cytometry analysis. Quantification of BCL11B expression on both mRNA and protein level was measured with quantitative realtime RT-PCR and western blot analysis before and after IFN_α treatment. Immunofluorescence analysis was used to observe the BCL11B expression on Hut-78 cell before and after IFN_α treatment. Results IFN_α significantly inhibited the growth of Hut78 cells. The effect was concentration dependent and duration dependent with the lowest growth rate at the time point of 48 hours. Meanwhile, IFN_α induced cell apoptosis, also in a concentration dependent way, with ceils treated with the highest concentration demonstrated the highest apoptosis rate. Furthermore, 10 000U/ml IFN_α incubated cells 3,6,9,12h time point, the BCL11B mRNA was significantly reduced. Specially, the BCL11B mRNA expression was at lowest point at 6h time point. 10 000U/ml IFN_α incubated cells 6,12,24h time point, the BCL11B protein also significantly reduced. The BCL11B protein expression decreased to a minimum at 12h time point. Conclusion IFN_α may exert its therapeutic effects on CTCL by directly inhibiting cell proliferation and inducing cell apoptosis. IFN_α may induce cell apoptosis and resensitize CTCL cells to chemotherapy by suppressing the expression of BCL11B gene.