肿瘤相关抗原肽与低剂量全身照射的协同抑瘤作用  

Low dose radiation enhancing inhibitory effect of tumor-associated antigen peptide extract on H-22 hepatocarcinoma

作　　者：孙祖玥[1] 付静宜[1] 刘建香[2] 付士波[3] 李修义[3] 刘树铮[3] 赵勇[1] 龚守良[3] 

机构地区：[1]中国科学院动物研究所生物膜与膜生物工程国家重点实验室移植生物学研究组,北京100080 [2]中国疾病预防控制中心辐射防护与核安全医学所 [3]吉林大学卫生部放射生物学重点实验室

出　　处：《中华放射医学与防护杂志》2005年第3期248-251,共4页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的观察低剂量X射线照射对小鼠肝癌H-22细胞膜相关抗原肽(TAP)提取物的抑瘤作用及免疫学功能的影响,为低剂量辐射(LDR)与肿瘤疫苗联合治疗肿瘤提供实验依据。方法采用微酸洗脱法制备相对分子质量≤3×106的细胞膜TAP提取物,先给予小鼠75mGyX射线全身照射,12h后以TAP提取物皮下免疫小鼠,检测脾细胞CD3、CD69和TCRαβ表面标记、脾T细胞亚组百分数的变化、脾细胞ConA反应性、IL-2和IFN-γ活性、CTL杀伤活性的变化及抑瘤效应。结果小鼠经TAP提取物免疫后,移植肿瘤的发生率降低,肿瘤平均出现时间延迟,生长速度减慢;脾细胞CD3分子和CD69分子的表达显著升高,脾细胞ConA反应性、IFNγ分泌活性和CTL杀伤活性显著增强,IL-2分泌增多。而同时给予LDR的小鼠不仅上述功能不同程度增强,脾CD8+细胞百分数显著增高。结论LDR与细胞膜TAP具有协同抑瘤作用,细胞免疫力的明显增强可能为其机制之一。Objective To determine whether there is synergically inhibitory effect of low dose radiation (LDR) and tumor-associated antigen peptides (TAP) on tumor growth in vivo, which may provide experimental basis for potential clinical co-application of these two approaches to treat cancers. Methods TAP extract (MW≤3×10~6) from tumor cell membrance was prepared with mild acid elution method, as reported. The mice were whole-bodily irradiated with 75 mGy X-rays 12 h before immunization with TAP extract. After immunization, the levels of CD3, CD69,TCRαβ cells and T cell subsets in the spleen were detected with FACS. The tumor growth rate was estimated, and the responses to Con A, the cytokine productions and CTL activities of splenocytes were also analyzed 7 d after immunization with TAP. Results The present experimental results showed that the TAP extract significantly reduced the incidence of the transplanted tumor, delayed the average appearing time and decreased the growth speed of the tumor. The response of splenocytes from mice immunized with TAP extract to Con A increased significantly compared with that in the control group.Irradiation with 75 mGy X-rays 12 h before immunization further enhanced the inhibitory effect of TAP extract on tumor growth, and increased the percentage of CD8^+ splenocytes. Conclusion These results suggest that whole-body irradiation with LDR exerts a synergic inhibitory effect with TAP on tumor growth in vivo,in which enhanced cellular immune responses may be involved. ;

关 键 词：协同抑瘤作用 抗原肽 肿瘤相关 低剂量辐射(LDR) CTL杀伤活性 低剂量X射线照射 X射线全身照射 CD8^+细胞 IFN-γ 相对分子质量 CD69 IL-2 免疫学功能 75mGy T细胞亚组 CD3分子 细胞免疫力 提取物 TAP 脾细胞 细胞膜 H-22 

分 类 号：R73-36[医药卫生—肿瘤]