目的：研究过表达IL-18 基因对人结直肠癌（colorectal cancer，CRC）HCT-116 细胞体内外增殖的影响及其可能的机制。方法：构建含人IL-18 基因片段的载体，采用慢病毒转染法获得稳定过表达人IL-18 的CRC HCT-116 细胞株HCT-116/IL-18，CCK-8 法检测HCT-116/IL-18 细胞与野生型HCT-116 细胞的增殖，Western blotting 检测两组细胞内IL-18、Cyclin D1、增殖细胞核抗原（PCNA）、DNA损伤修复酶（PARP）蛋白的表达。将HCT-116、HCT-116/IL-18 细胞分别接种于裸鼠左右两侧腋下，观察成瘤性及移植瘤的生长情况，免疫组化法检测移植瘤组织中IL-18 及PCNA的表达。结果：IL-18 基因在HCT-116 细胞内过表达，可延缓HCT-116 的增殖（P<0.05 或P<0.01）；与HCT-116 细胞相比，HCT-116/IL-18 细胞内PARP表达明显增强，PCNA、Cyclin D1 表达减弱（P<0.01）。HCT-116/IL-18 细胞系在裸鼠体内成瘤率明显降低，成瘤率为43%，与对照组比较其移植瘤成瘤时间晚、生长慢、肿块小,且HCT-116 / IL-18 异种移植瘤PCNA蛋白表达下调（P<0.01）。结论：过表达IL-18 基因对HCT-116 细胞生长增殖具有抑制作用，其机制可能与IL-18调控细胞周期和促进DNA损伤有关。

Objective: To investigate the effects of interleukin-18 over-expression on the in vitro and in vivo proliferation of human colorectal cancer (CRC) HCT-116 cells. Methods: A recombinant lentivirus vector containing human IL-18 gene fragment was constructed.Then theCRC HCT-116 cell line stably expressing human IL-18 (HCT-116/IL-18) was obtained by recombinant lentivirus transfection. In vitro proliferation of HCT-116/IL-18 cells and wild-type HCT-116 cells was determined by CCK-8 method. The expressions of IL-18, Cyclin D1, proliferating cell nuclear antigen (PCNA) and DNA damage repair enzyme (PARP) were detected by Western blotting. HCT-116 and HCT-116/IL-18 cells were inoculated into left and right axillas of Balb/c nude mice, respectively. Then the tumorigenicity and the growth of transplanted tumor were observed. The expressions of IL-18 and PCNA in xenograft tissues were detected by immunohistochemistry analysis. Results: IL-18 gene over-expression in HCT-116 cells could delay the proliferation of HCT-116 cells (P<0.05 or P<0.01). PARP expression was increased significantly and PCNA, Cyclin D1 expression were decreased in HCT-116/IL-18 cells as compared to that of HCT-116 cells (P<0.01).The tumorigenicity of HCT-116/IL-18 cell was significantly decreased in nude mice with a tumor-formation rate of 43%; Compared with control group, HCT-116/IL-18cell line had a longer tumorigensis time,slower growth and smaller tumor volume; moreover, PCNA protein expression was down-regulated in HCT-116/IL-18 xenograft tissue-sas shown by immunohistochemistry analysis (P<0.01). Conclusion: IL-18 over-expression inhibited the growth and proliferation of HCT-116cells both in vitro andin vivo, and the mechanism might be related with IL-18 regulating cell cycle and promotingDNAdamage.

国家自然科学青年基金资助项目（No.81201765）；河南省高校重点科研资助项目（No.15A320063, No.16A310022）；河南省骨干青年教师培养计划(No.2016GGJS-105)；新乡医学院研究生科研创新支持计划资助项目(No.YJSCX201616Y)