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  

The suppression of IL-24 on pancreatic cancer mediated by tumor-targeting oncolytic adenovirus in immune-competent mice

作　　者：徐彬[1] 钱明平[1] 杨庭松[1] 宋振顺[1] 刘新垣[2] 周波[1] 

机构地区：[1]同济大学附属第十人民医院普外科,上海200072 [2]上海生命科学研究院生物化学与细胞生物学研究所

出　　处：《中华肝胆外科杂志》2014年第6期457-460,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金（81001007）;同济大学附属第十人民医院优秀青年基金资助（10RQ105）

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Pane02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.

关 键 词：胰腺癌 溶瘤腺病毒 白细胞介素-24 T淋巴细胞 细胞因子 

分 类 号：R735.9[医药卫生—肿瘤]