IL-2和IL1-2基因联合治疗小鼠头颈鳞癌的实验研究

Combined IL-2 and IL-12 gene therapy for murine head and neck squamous cell carcinoma

目的 观察白细胞介素 2 (IL 2 )基因与白细胞介素 12 (IL 12 )基因联合治疗小鼠头颈鳞癌的疗效。方法 建立小鼠头颈鳞癌动物模型 ,在荷瘤部位将脂质体包裹的IL 2基因和IL 12基因直接注入肿瘤中 ,观察肿瘤大小变化 ,并检测此两种基因在肿瘤细胞中的蛋白表达情况、小鼠脾脏自然杀伤细胞 (NK)和细胞毒T淋巴细胞 (CTL)活性。结果 IL 2基因和IL 12基因联合治疗组 ,肿瘤生长明显受抑制 ,疗效显著优于单独治疗组和对照组 (P <0 .0 1)。在注射有IL 2、IL 12基因的肿瘤组织中 ,其相对应的IL 2、IL 12蛋白水平明显升高 ,小鼠脾细胞NK活性和CTL杀伤活性增强。结论 IL 2、IL 12基因治疗可抑制小鼠头颈鳞癌生长 ,提高机体的抗肿瘤免疫应答。二者联合应用 ,可产生协同效应并加强其抗肿瘤效果。

Objective To evaluate the efficacy of combined interleukin(IL) 2 gene and IL 12 gene the rapy in murine model with head and neck squamous cell carcinoma (HNSCC). Methods HNSCC model was established in the mouth floor of C3H/HeJ mice with SCCⅦ cell line. Lipid IL2 and lipid IL12 plasmid complexes were introduced either alone or in combination into the tumor by direct intratumor gene injection. Tumor size was measured before and after the treatment to evaluate the response of the dif ferent treatment and control groups. Enzyme linked immunosorbent assay (ELISA) was used to measure the IL 2 and IL 12 expression. Lactic dehydrogenase (LDH) assay was used to evaluate the activity of Cytotoxic T Lymphocyte (CTL) and n atural killer (NK) cells. Results Growth of HNSCC was significantly inhibited in combined IL 2 and IL 12 gene th erapy group as compared with the other groups ( P <0.01). Increased level of I L 2 and IL 12 protein expression was found in both combined and single treatme nt groups . Greater activity of CTL and NK was also observed in these two groups as compared with the controls. Conclusion Both IL 2 and IL 12 gene therapy is able to inhibit the growth of HNSCC and induce the host antitumor immune response efficiently in the murine m odel. Combination of the two in gene therapy may be additive or synergistic in a ntitumor effect. [WT5'HZ