氟达拉滨联合瘤苗抗肿瘤生物治疗作用的实验研究  

Empirical study of enhancing anti-tumor biotherapy through fludarabine and tumor vaccine

作　　者：柴晓菲[1] 高全立[1] 许林平[1] 买玲[1] 

机构地区：[1]河南省肿瘤医院病理科,郑州450008

出　　处：《中国医药生物技术》2008年第6期425-429,共5页Chinese Medicinal Biotechnology

基　　金：河南省社会公益项目科研专项(064130202)

摘　　要：目的探讨氟达拉滨对小鼠CD4+CD25+Treg细胞的影响,同时研究其抗肿瘤作用。方法氟达拉滨或生理盐水分别腹腔注射10只小鼠,用流式细胞术检测CD4+CD25+Treg细胞相对量。氟达拉滨或生理盐水分别腹腔注射10只小鼠,4d后用丝裂霉素灭活的肿瘤细胞免疫小鼠,观察小鼠抗肿瘤的能力(观察肿瘤发生率和出瘤时间);用乳酸脱氢酶杀伤实验进一步验证氟达拉滨可增强CTL的杀伤活性。结果氟达拉滨组CD4+CD25+Treg细胞占淋巴细胞百分比为(1.150±0.256)%,对照组为(1.488±0.270)%,氟达拉滨组明显低于对照组(P<0.05);氟达拉滨+接种瘤苗组、生理盐水+接种瘤苗组、氟达拉滨+未接种瘤苗组和生理盐水+未接种瘤苗组小鼠第13天肿瘤发生率分别为10%、30%、50%和70%,两两间差异均有统计学意义(P<0.05);氟达拉滨+接种瘤苗组、生理盐水+接种瘤苗组、氟达拉滨+未接种瘤苗组和生理盐水+未接种瘤苗组小鼠分别在接种后第13天、第10天、第8天和第5天发现出瘤现象;对照组的肿瘤生长曲线较为陡直,氟达拉滨组的生长曲线较为平缓。氟达拉滨联合瘤苗接种组和单纯瘤苗接种CTL的活性分别为24.425±13.544和17.575±10.260,两者间差异有统计学意义(P<0.05)。结论低剂量氟达拉滨降低CD4+CD25+Treg细胞,使其抗肿瘤免疫作用增强,联合接种灭活瘤苗进一步增强抵抗肿瘤攻击的能力。Objective To studythe effects of fludarabine on CD4＋CD25＋Treg T regulatory cells and study its anti-tumor ability in mice. Methods Fludarabine or saline were injected i.p. into l0 mice. And the relative count of CD4＋CD25＋Treg cells was detected by flow cytometry; fludarabine or saline was injected i.p. into 10 mice. Four days later, the mice were vaccinated by mitomycin inactivated tumor cells and the tumor occurring time, tumor volume and survival time were observed. And the anti-tumor ability was examined by attacking tumor cells and LDH assay. Results The percentage of CD4＋CD25＋Treg cells in total lymphocyte cells had significant difference between control group （1.150 ± 0.256）% and fludarabine group （1.488 ± 0.270）% （P 〈 0.05）. After the RMA tumor cells attacked, the incidences of tumors in mice of fludarabine ＋ inoculation tumor vaccine group, NS ＋ inoculation tumor vaccine group, fludarabine ＋ no inoculation tumor vaccine group and NS ＋ no inoculation tumor vaccine group were 10%, 30%, 50% and 70% respectively; After inoculation, murine tumorigenesis in fludarabine ＋ inoculation tumor vaccine group, NS ＋ inoculation tumor vaccine group, fludarabine ＋ no inoculation tumor vaccine group and NS ＋ no inoculation tumor vaccine group were 13d, 10d, 8d and 5d respectively. The CTL activities of the fludarabine ＋ inoculation tumor vaccine group was higher than that of the NS ＋ inoculation tumor vaccine group （24.4250 ± 13.5443 vs 17.5750± 10.2601, P〈 0.05）. Conclusion A low dose of fludarabine decreased mouse CD4＋CD25＋Treg cells, in combination with tumor vaccine, it could enhance the anti-tumor ability.

关 键 词：癌症疫苗 生物疗法 T淋巴细胞 调节性 

分 类 号：R730.5[医药卫生—肿瘤]