中文摘要：

背景与目的已有的研究表明肺癌细胞可通过上调Fas配体（FasL）表达、借助FasL/Fas凋亡途径反杀伤Fas阳性肿瘤浸润淋巴细胞（TIL）,主动逃避免疫监视,导致肿瘤局部抗肿瘤免疫下降。本研究旨在探讨遗传修饰调节肺癌细胞FasL基因表达对T细胞凋亡的影响。方法通过质粒载体,将体外化学合成的靶向FasL的小干扰RNA（siRNA）直接转染人大细胞肺癌细胞株H460,采用RT-PCR和Westernblot技术观察肺癌细胞FasLmRNA及蛋白表达的变化及其诱导T细胞凋亡的改变。结果化学合成的靶向FasL基因的siRNA能够显著下调肺癌细胞H460FasLmRNA和蛋白表达水平,产生序列特异性干扰效果。RNA干扰（RNAi）抑制H460细胞FasL表达后可以降低和逆转肺癌细胞诱导的T细胞凋亡,恢复T细胞增殖能力。结论FasL是一新的具有发展前途的肺癌基因治疗靶位。

英文摘要：

Background and objective Lung cancer cells can upregulate the expression of Fas ligand （FasL） and counterattack tumor-infiltration lymphocyte （TIL） expressing Fas via the FasL/Fas pathway, therefore escape from immunosurveillance and impair local anti-tumor immune capacity. The aim of this study is to investigate the effects of reducing FasL expression on T cell apoptosis in lung cancer cell line H460 via small interfering RNA （siRNA） technology. Methods In vitro chemically synthesized siRNA targeting FasL as well as constructed plasmid vector were transfected into H460 cells, wherein the interfering effect and alterations in T cell apoptosis were observed. Results Sequence-specific interfering effect was detected at RNA and protein levels by RT PCR and Western blot in the H460 si group, and the reduction of FasL expression was capable of rescuing T cell apoptosis induced by lung cancer cells. Conclusion FasL can be utilized as a new target in gene therapy of lung cancer.