靶向融合肽IL-4Rα-lytic对原发性渗出性淋巴瘤的抑制作用  

Inhibitory effect of targeted fusion peptide IL-4Rα-lytic on primary effusion lymphoma

作　　者：郑响 陈小亭 蔡启良 魏芳 ZHENG Xiang;CHEN Xiaoting;CAI Qiliang;WEI Fang(Sheng Yushou Center of Cell Biology and Immunology,School of Life Sciences and Biotechnology,Shanghai Jiaotong University,Shanghai 200240,China;Key Laboratory of Medical Molecular Virology of Ministries of Education and Health,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China)

机构地区：[1]上海交通大学生命科学技术学院盛毓绶细胞与免疫学研究中心,上海200240 [2]复旦大学基础医学院教育部/卫生部医学分子病毒学重点实验室,上海200032

出　　处：《中国肿瘤生物治疗杂志》2022年第3期175-180,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.81772166)

摘　　要：目的:探讨靶向融合肽IL-4Rα-lytic对卡波西肉瘤相关疱疹病毒(KSHV)阳性原发性渗出性淋巴瘤(PEL)细胞的体内外杀伤作用及其安全性。方法:应用MTT法检测IL-4Rα-lytic对KSHV阳性PEL细胞BCBL-1和BCP-1的杀伤能力。通过FCM检测IL-4Rα-lytic诱导KSHV阳性PEL细胞凋亡的情况。建立BCBL-1细胞小鼠移植瘤模型,连续3周(3次/周)腹腔注射IL-4Rα-lytic后,通过活体生物发光成像技术评估IL-4Rα-lytic对小鼠体内BCBL-1细胞移植瘤的抑制效果,并通过H-E染色和全血分析法检测其毒副作用。结果:靶向融合肽IL-4Rα-lytic在体外对两种KSHV阳性PEL细胞BCBL-1和BCP-1均有选择性杀伤作用(均P<0.01),并且可以在短时间内发挥杀伤作用(均P<0.01)。靶向融合肽IL-4Rα-lytic可诱导KSHV阳性PEL细胞BCBL-1和BCP-1凋亡(均P<0.05)。靶向融合肽IL-4Rα-lytic显著抑制BCBL-1细胞小鼠移植瘤的生长,与对照组比较差异具有统计学意义(P<0.05),并且无明显的器官毒性(均P>0.05),同时不会造成体质量异常(P>0.05)。结论:靶向融合肽IL-4Rα-lytic在体内外均显著抑制KSHV阳性PEL细胞的生长,且无明显毒副作用,有望为PEL的治疗提供一种新的治疗方案。Objective:To explore the in vitro and in vivo cytotoxicity of fusion peptide IL-4Rα-lytic against Kaposi sarcomaassociated herpesvirus(KSHV)positive primary effusion lymphoma(PEL)cells and its safety.Methods:The cytotoxicity of IL-4Rα-lytic against KSHV+PEL cells(BCBL-1 and BCP-1)was measured by MTT assay.The IL-4Rα-lytic induced apoptosis of KSHV+PEL cells was analyzed by FCM.A BCBL-1 cell xenograft mice model was constructed.IL-4Rα-lytic was intraperitoneally injected for three consecutive weeks(3 times/week),and the inhibitory effect of IL-4Rα-lytic on the growth of BCBL-1 cell xenograft in mice was evaluated with in vivo bioluminescence imaging technology.Moreover,the toxic side effect was analyzed using H-E staining and whole blood cell analysis.Results:Fusion peptide IL-4Rα-lytic had a selective cytotoxicity against KSHV+PEL BCBL-1and BCP-1 cells(all P<0.01)and could rapidly kill KSHV+PEL cells(all P<0.01).IL-4Rα-lytic could induce the apoptosis of KSHV+PEL BCBL-1 and BCP-1 cells(all P<0.05).IL-4Rα-lytic significantly inhibited the growth of BCBL-1 cell xenograft in mice(P<0.05)without causing obvious organ toxicity(all P<0.05)and abnormal changes in body weight(P>0.05).Conclusion:Fusion peptide IL-4Rα-lytic can significantly inhibit the growth of KSHV+PEL cells in vivo and in vitro without obvious toxic side effects,which is expected to provide a novel strategy for the treatment of PEL.

关 键 词：原发性渗出性淋巴瘤 靶向融合肽 卡波西肉瘤相关疱疹病毒 IL-4Rα 裂解肽 

分 类 号：R733.1[医药卫生—肿瘤]