靶向溶瘤腺病毒介导的IL-24对有免疫功能小鼠胰腺癌移植瘤生长的抑制

摘要

目的 探讨靶向溶瘤腺病毒介导的IL-24(ZD55-IL-24)对有免疫功能小鼠的胰腺癌移植瘤生长的抑制作用.方法 体外采用结晶紫染色观察ZD55-IL-24.对胰腺癌细胞Panc02的生长抑制作用.体内采用肿瘤生长曲线、成瘤率曲线、TUNEL凋亡检测、细胞毒T淋巴细胞(CTL)杀伤试验和细胞因子检测评价ZD55-IL-24对小鼠胰腺癌的生长抑制作用.结果 ZD55-IL-24体外能抑制胰腺癌细胞生长.体内实验表明,与ZD55-EGFP组或者PBS组比较,ZD55-IL-24组的肿瘤成瘤率低,肿瘤生长速度更慢.ZD55-IL-24不仅能诱导肿瘤细胞凋亡,还能通过诱导CTL杀伤胰腺癌细胞并通过上调血浆γ-IFN和IL-6水平而产生抗肿瘤免疫作用.结论 ZD55-IL-24在有免疫功能的小鼠上能产生抗肿瘤免疫和抑制胰腺癌移植瘤生长.%Objective To investigate whether IL-24 can inhibit the growth of pancreatic cancer in immune-competent mice,which could be mediated by tumor-targeting oncolytic adenovirus (ZD55-IL-24).Methods Crystal violet staining assay was used to evaluate the anti-proliferative influence of ZD55-IL-24 on Panc02.The tumor growth curve,the tumor formation curve,TUNEL assay,cytotoxic T lymphocyte (CTL) killing assay and serum cytokines detection were used to assess anti-tumor efficacy of ZD55-IL-24 for pancreatic cancer in immune-competent mice.Results ZD55-IL-24 significantly inhibited the growth of pancreatic cancer cells in vitro.Lower tumor formation and slower tumor growth were identified in ZD55-IL-24 group,compared with ZD55-EGFP group or PBS group.ZD55-IL-24 induced pancreatic cancer cells'apoptosis,and mediated anti-cancer immunity by increasing killing responses of CTL to cancer cells and up-regulating serum γ-IFN and IL-6 levels.Conclusion ZD55-IL-24 can induce anti-tumor immunity and suppress pancreatic cancer growth in immune-competent mice.