rNDV-IL-2和rNDV-TRAIL治疗肿瘤的协同作用  

Synergistic effects of rNDV-IL-2 and rNDV-TRAIL on cancer therapy

作　　者：李思明 盛美琳 吴毓斌 白福良 LI Siming;SHENG Meilin;WU Yubin;BAI Fuliang(College of Pharmacy,Harbin University of Commerce,Harbin 150076,China;Lubin Environmental Technology(Shanghai)Co,Shanghai 200000,China)

机构地区：[1]哈尔滨商业大学药学院,哈尔滨150076 [2]鹭滨环保科技(上海)有限公司,上海200000

出　　处：《哈尔滨商业大学学报（自然科学版）》2024年第3期273-280,共8页Journal of Harbin University of Commerce：Natural Sciences Edition

基　　金：黑龙江省自然科学基金(YQ2021H002)。

摘　　要：通过比较rNDV表达的白细胞介素-2(IL-2)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)治疗肿瘤的效果,并进一步探讨联合应用rNDV-IL-2和rNDV-TRAIL是否在肿瘤治疗中产生协同效应.体外培养H22肝癌细胞株和B16-F10黑色素瘤细胞株,并建立小鼠H22肝癌和B16-F10黑色素瘤动物模型,注射rNDV-IL-2和rNDV-TRAIL病毒进行治疗.同时注射人IL-2和TRAIL的重组新城疫病毒(rNDV-IL-2+rNDV-TRAIL)显著提高了rNDV通过诱导细胞凋亡来杀伤肿瘤细胞的能力.小鼠肝癌和恶性黑色素模型鼠的治疗实验表明,与对照相比,rNDV-IL-2或rNDV-TRAIL显著抑制了肿瘤的生长并延长荷瘤小鼠的存活.与rNDV-IL-2和rNDV-TRAIL治疗组相比较,rNDV-IL-2+rNDV-TRAIL联合治疗进一步增强了rNDV的抗肿瘤功效,并进一步延长了动物的存活时间.动物实验结果还表明,荷瘤鼠rNDV-IL-2和rNDV-IL-2+rNDV-TRAIL治疗后均可诱导系小鼠体内的CD4^(+)细胞和CD8^(+)细胞的增殖,并且rNDV-IL-2+rNDV-TRAIL联合治疗表现出明显的协同作用.rNDV-IL-2+rNDV-TRAIL联合治疗在体内外均能够明显抑制肿瘤增殖,较单一应用rNDV-IL-2或rNDV-TRAIL有更好的效果,值得进一步深入研究.Recombinant Newcastle disease virus(rNDV)as oncolytic agent has been shown to be effective for cancer therapy.This paper compared the efficacy of RNDV-expressed interleukin-2(IL-2)and tumor necrosis factor-associated apoptosis-inducing ligand(TRAIL)in tumor therapy,and further explored whether the combination of rNDV-IL-2 and rNDV-TRAIL has a synergistic effect in tumor therapy.H22 hepatocellular carcinoma cell line and B16-F10 melanoma cell line were cultured in vitro,and mouse H22 hepatocellular carcinoma and B16-F10 melanoma animal models were established.Recombinant Newcastle Disease virus(rNDV-IL-2+rNDV-TRAIL)injected with both human IL-2 and TRAIL significantly improved the ability of rNDV to kill tumor cells by inducing apoptosis.Therapeutic experiments in mouse models of liver cancer and malignant melanin showed that rNDV-IL-2 or rNDV-TRAIL significantly inhibited tumor growth and prolonged survival of tumor-bearing mice compared with controls.Compared with rNDV-IL-2 and rNDV-TRAIL treatment groups,rNDV-IL-2+rNDV-TRAIL combined treatment further enhanced the anti-tumor efficacy of rNDV and extended the survival time of animals.Animal experiments also showed that both rNDV-IL-2 and rNDV-IL-2+rNDV-TRAIL treatment could induce the proliferation of CD4^(+)and CD8^(+)m cells in tumor-bearing mice,and the combined treatment of rNDV-IL-2+rNDV-TRAIL showed obvious synergistic effect.

关 键 词：重组新城疫病毒 癌症治疗 白细胞介素-2 肿瘤坏死因子相关凋亡诱导配体 协同治疗 

分 类 号：Q291[生物学—细胞生物学]