[关键词]
[摘要]
目的:探讨次级淋巴组织趋化因子(seccondary lymphoid tissue chemokine, SLC)和CpG寡聚脱氧核苷酸(CpG oligodeoxynucleotide, CpGODN)联合应用对小鼠移植黑素瘤的治疗效果及其可能机制。方法:制备SLCFc融合蛋白,体外检测SLCFc对小鼠淋巴细胞的趋化效应。建立小鼠黑素瘤移植模型,随机分生理盐水对照组、CpGODN组、SLCFc组以及SLCFc+CpGODN组共4组。观察治疗后各组小鼠肿瘤的生长情况,流式细胞术检测移植瘤组织中淋巴细胞的种类和浸润情况。结果:成功制备SLCFc蛋白,SLCFc对小鼠淋巴细胞具有剂量依赖性(0.03、0.3和3 μg/L)趋化作用。瘤内注射SLCFc和(或)CpGODN明显抑制肿瘤的生长,联合治疗组瘤体明显小于对照组(P<0.01),并且小鼠存活时间也明显延长。联合治疗组瘤体内CD4+、CD8+T淋巴细胞和CD11c+树突状细胞较对照组显著增多(P<0.05,P<0.01),并且其肿瘤引流淋巴结也明显增大。结论:SLC和CpGODN联合应用对小鼠移植黑素瘤有抑制作用,其机制与趋化CD4+T、CD8+T细胞和促进DCs增殖有关。
[Key word]
[Abstract]
Objective:To study the therapeutic effect of secondary lymphoid tissue chemokine (SLC) combined with CpG oligodeoxynucleotide (CpGODN) in treatment of implanted mouse melanoma and the possible mechanism. Methods:SLCFc fusion protein was prepared and its chemotaxis of lymphocytes was detected by chemotaxis assay. Implanted melanoma mouse models were established and randomly divided into 4 groups: control group, SLCFc group, CpGODN group, and SLCFc+CpGODN group. The growth of implanted tumors in each group was observed after treatment. Subtype and infiltration of lymphocytes in implanted tumor tissues were examined by flow cytometry. Results:SLCFc protein was successfully prepared, and it dosedependently attracted lymphocytes (0.03, 0.3, and 3 μg/L). Intratumor injection SLCFc and CpGODN alone or in combination significantly inhibited growth of B16implanted tumors. Tumor size in SLCFc+CpGODN group was significantly smaller than that in control group (P<0.01), and animals in SLCFc+CpGODN group survived longer. Tumorinfiltrated CD4+ T, CD8+ T, and dendritic cells (DCs) in SLCFc+CpGODN group were markedly increased as compared with those in control group (P<0.05), and tumor draining lymph nodes were dramatically enlarged. Conclusion:SLC combined with CpGODN can inhibit the growth of implanted melanoma by attracting CD4+ T and CD8+ T and promoting proliferation of DCs.
[中图分类号]
[基金项目]
厦门市科技局计划指导性项目(No.3502z20089020)