【摘要】 目的 探讨卷曲跨膜受体蛋白2(FZD2)在小鼠舌鳞癌中的功能，及其对细胞毒性T淋巴细胞相关抗原4(CTLA4)单抗治疗的影响。方法 细胞实验：SCCVII小鼠舌鳞癌细胞分为空白对照组(转染LV-kdCon)和实验组(转染LV-kdFZD2)。用细胞计数试剂盒-8(CCK-8)检测细胞增殖能力，用Transwell小室实验检测迁移能力，用人脐静脉内皮细胞验证血管生成能力。动物实验：雌性C3H/He小鼠构建荷瘤小鼠模型，分为对照组[给予磷酸盐缓冲液注射(PBS)]、kdFZD组(接种实验组细胞并给予等量PBS注射)、αCTLA4组(小鼠皮下接种空白对照组细胞并给予CTLA4单抗注射)和kdFZD+αCTLA组(小鼠皮下接种实验组细胞并给予CTLA4单抗注射)。用定量聚合酶链反应检测肿瘤组织mRNA相对表达水平，测量肿瘤体积和质量。结果 空白对照组和实验组细胞中FZD2 mRNA相对表达水平分别为1.01±0.18和0.52±0.18,细胞迁移数为(466.70±44.10)和(160.00±26.46)个，人脐静脉内皮上皮细胞形成的小管分支节点数分别为(108.70±6.35)和(84.33±10.02)个，总毛细血管长度分别为(20 235±2 229)和(16 549±338)μm,组间比较，在统计学上差异均有统计学意义(P<0.05,P<0.01)。对照组、kdFZD组、αCTLA4组和kdFZD+αCTLA组肿瘤体积分别为(449.50±114.80)、(131.10±13.49)、(83.62±26.47)和(2.45±0.91) mm~3,肿瘤质量分别为(0.78±0.11)、(0.22±0.06)、(0.13±0.02)和(0.03±0.01) g,组间比较，在统计学上差异均有统计学意义(P<0.001,P<0.000 1)。结论 FZD2可作为潜在的舌鳞癌治疗靶点，有望成为舌鳞癌辅助免疫治疗优化的关键分子。更多还原

【Abstract】 Objective To investigate the function of Frizzled 2(FZD2) in mouse tongue squamous cell carcinoma and its effect on cytotoxic T lymphocyte-associated antigen 4(CTLA4) monoclonal antibody. Methods Cell experiment: SCCVII mouse tongue squamous cell carcinomq cells were divided into blank control group(transfected LV-kdCon) and experimental group(transfected LV-kdFZD2). Cell proliferation ability was detected by cell counting kit-8(CCK-8); migration ability was detected by Transwell cell assay; and angiogenesis ability was verified by human umbilical vein endothelial cells. Animal experiments: Female C3H/He mice were constructed with tumor bearing mice model. Mice were divided into control group [injected with phosphate buffer solution( PBS) ],kd FZD group( inoculated with experimental cells and injected with an equal amount of PBS),αCTLA4 group( inoculated with blank control cells subcutaneously and injected with CTLA4monoclonal antibody) and kd FZD + αCTLA group( inoculated with experimental cells subcutaneously and injected with CTLA4 monoclonal antibody). The mRNA expression of tumor tissue was detected by quantitative polymerase chain reaction( q PCR),and the tumor volume and mass were measured. Results The relative expression levels of FZD2mRNA in the control group and the experimental group were 1. 01 ± 0. 18 and 0. 52 ± 0. 18; the cell migration numbers were 466. 70 ± 44. 10 and 160. 00 ± 26. 46; the number of branch nodes of human umbilical vein endothelial cells were108. 70 ± 6. 35 and 84. 33 ± 10. 02; the total capillary length were( 20 235 ± 2 229) and( 16 549 ± 338) μm,respectively,with statistical significance( P < 0. 05,P < 0. 01). The tumor volumes of control group,kd FZD group,αCTLA4 group and kd FZD + αCTLA group were( 449. 50 ± 114. 80),( 131. 10 ± 13. 49),( 83. 62 ± 26. 47) and( 2. 45 ± 0. 91) mm3; the tumor weights were( 0. 78 ± 0. 11),( 0. 22 ± 0. 06),( 0. 13 ± 0. 02) and( 0. 03 ± 0. 01) g,respectively,and the differences were statistically significant( P < 0. 001,P < 0. 000 1). Conclusion FZD2 can be used as a potential therapeutic target for tongue squamous cell carcinoma and is expected to be a key molecule in the optimization of adjuvant immunotherapy for tongue squamous cell carcinoma.更多还原