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 sarcoma- associated 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-1 and 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.

R733.4；R730.54

国家自然科学基金资助项目（No.81772166）