白细胞介素-2基因联合放疗对小鼠头颈鳞癌治疗作用的研究

目的：观察白细胞介素-2（IL-2）基因联合放疗对小鼠头颈鳞癌的抗肿瘤作用。方法：将25只小鼠平分为5组。利用SCCⅦ细胞株在C3H/HeJ小鼠口底建立头颈鳞癌荷瘤动物模型,IL-2组和联合组在荷瘤部位直接注射IL-2基因;EP组和对照组分别注射无目的基因的空载体和PBS,次日联合组与放疗组给予2Gy直线加速器的局部肿瘤放疗。4d后重复IL-2基因治疗,观察肿瘤治疗前后大小变化;检测肿瘤组织中CD4^ ,CD8^ 的表达,IL-2的分泌水平及自然杀伤细胞（NK）和细胞毒T淋巴细胞（CTL）的活性。结果：联合组肿瘤生长明显受抑制,疗效显著优于IL-2组,放疗组,EP组和对照组,IL-2组中,小鼠IL-2分泌水平明显升高,脾细胞NK活性和CTL杀伤活性增强,肿瘤组织内可见大片坏死,并含有大量的CD4^ ,CD2^ 淋巴细胞浸润,结论：IL-2基因治疗可提高肿瘤局部和全身的抗肿瘤免疫应答。能加强放疗的抗肿瘤效果。

Antitumour study with combined IL-2 gene therapy and radiation for head and neck squamous cell carcinoma

OBJECTIVE: To assess the efficacy of combination therapy with IL-2 gene transfer and radiation in an immunocompetent murine model that parallel more closely the clinical therapy of head and neck Squamous cell carcinoma(HNSCC). METHOD: Tumors were established in the floor of mouth in C3H/HeJ mice with SCC VII cell line. Lipid-DNA complexed (lipoplexes) by using polycationic liposome-Mediated transduction for HNSCC were transducted in tumor-bearing mouse by direct intratumoral gene transfer. The local tumor radiation with 2 Gy were done in second day. Tumor size were measured before and after the treatment as compared to different single treatment groups and the controls. After tumors were subcultured, the supernatants were collected for IL-2 expression by enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and cytotoxic T-lymphocyte (CTL) activity were also assayed by LDH method. CD4+ and CD8+ T-lymphcyte in tumour tissues were examined by immunohistochemistry. RESULT: HNSCC tumor growth was significantly inhibited after a combined IL-2 gene and radiation therapy as compared to the controls. Increased secreted levels of IL-2 protein expression were found in combined and single IL-2 gene treated groups. The combination and IL-2 gene treated groups produced greater activation of CTL and NK than the other groups. The significant CD4+ and CD8+ T lymphocyte infiltration was distributed in tumor tissues after IL-2 gene therapy. CONCLUSION: Combined IL-2 gene therapy and radiation could significantly inhibited HNSCC tumor growth in the murine model and efficiently induced antitumor immunity of the host.