将抗人P185 erbB2 scFv-Fc-IL-2融合蛋白（HFI）作用于人卵巢癌细胞株SKOV3细胞和人外周血单个核细胞（PBMC），通过体外实验阐明HFI调变肿瘤细胞表面分子和激活免疫效应细胞的抗肿瘤机制，为HFI临床应用提供实验依据。方法：MTT法检测细胞增殖、杀伤活性；流式细胞术观察细胞表面分子的表达水平；生物活性法检测细胞膜相关TNF杀伤活性；RT-PCR检测细胞穿孔素表达水平。结果： HFI处理后，未观察到对SKOV3细胞增殖活性的直接抑制作用；SKOV3细胞表面杀伤相关分子ICAM-1、Fas表达率分别由24.85%、0.53%增高到85.36%、59.19%（P<0.01)；人PBMC的增殖活性增强，CD3 + CD8 + T细胞和CD3 --CD1 + CD56 + NK细胞分别由24.37%、6.90%提高到38.80%、13.45%（ P <0.01)；CD25、LFA-1、FasL表达水平分别由399%、86.52%、5.02%提高到12.96%、99.06% 16.19%（P<0.01)；穿孔素基因、膜相关TNF均表达增强，LAK样、NK样杀伤活性在各效靶比时均明显增高（P<0.01)。结论： HFI提高SKOV3细胞杀伤相关分子ICAM-1、Fas表达水平，并且对人PBMC有明显的增殖活化作用，通过激活LFA-1/ICAM-1、Fas/FasL途径提高杀伤介质穿孔素和膜相关TNF的释放，增强LAK样、NK样杀伤活性。

To elucidate the mechanisms by which anti-P185 erbB2 scFv-Fc-IL-2 (HFI) modulates tumor surface molecules and activates immune effector cells in vitro. Methods: Ovarian Cancer Cell Line SKOV3 and human peripheral blood monocyte peripheral blood mononuclear cells (PBMC) were treated with HFI. MTT assay was used to detect the proliferation and cytotoxicity; flow cytometry assay was used to examine expression of surface molecules; bioassay was used to examine cytotoxicity of membrane-associated TNF; and perforin mRNA level was analyzed by RT-PCR assay. Results: HFI had no direct inhibitory effect on proliferation of SKOV3 cells. After HFI treatment, the expression levels of ICAM-1 and Fas on SKOV3 cells rose from 24.85% and 0.53% to 85.36% and 59.19%, respectively （ P <0.01). Besides, HFI significantly enhanced the proliferation of human PBMC. CD3+CD8+ T cells and CD3-CD16+CD56+ T cells rose from 2437% and 6.90% to 38.80% and 13.45%, respectively （ P <0.01). Expression levels of CD25, LFA-1, and FasL significantly increased from 3.99%, 86.52%, and 5.02% to 12.96%, 99.06%, and 16.19%, respectivly（P<0.01). Expression levels of Perforin and membrane-associated TNF were also up-regulated. Cytotoxicities of LAK and NK were both improved（P<0.01). Conclusion: HFI can enhance the expression of ICAM-1 and Fas in SKOV3 cells and has obvious activating effect on PBMC. HFI can up-regulate the expression level of LFA-1/ ICAM-1，Fas/ FasL, promote the release of TNF and perforin, and improve LAK and NK cytotoxicity.

山东省科技攻关基金资助项目（No.2004GG2202149）