设为首页 |加入收藏 |联系我们 |ENGLISH

 

首页

 

期刊概况

 

编委会

 

过刊浏览

 

特邀审稿

 

投稿指南

 

出版发行

 

联系我们

CpG ODN协同MAGE-3 抗原肽致敏DC疫苗对膀胱癌细胞BIU-87 的抑制作用[J].李秀真,薛庆节,路海,聂尚丹,王晖,李运清,赵龙玉,谭文彬.中国肿瘤生物治疗杂志,2018,(9):891~897.
CpG ODN协同MAGE-3 抗原肽致敏DC疫苗对膀胱癌细胞BIU-87 的抑制作用    点此下载全文    点此浏览HTML全文
李秀真  薛庆节  路海  聂尚丹  王晖  李运清  赵龙玉  谭文彬
济宁医学院病原生物学教研室,山东济宁 272067
基金项目:国家自然科学基金资助项目(No.31500056);山东省高等学校科技计划资助项目(No.J11LF03);济宁市科技助推新旧动能转换计划资助项目(No.2017SMNS001);济宁医学院青年教师科研扶持基金资助项目(JNo.Y2017KJ010)
DOI:10.3872/j.issn.1007-385X.2018.09.008
摘要:
      目的:探讨含未甲基化胞嘧啶鸟嘌呤(CpG)序列的细菌寡核苷酸(CpG oligodeoxynucleotide,CpG ODN)免疫佐剂在增强黑色素瘤抗原基因-3(melanoma antigen gene -3,MAGE-3)抗原肽致敏DC抗膀胱肿瘤细胞的作用及其分子机制。方法:采用Ficoll 法从健康志愿者HLA-A2 型外周血中分离单个核细胞,常规方法诱导培养制备成熟DC。MTT法检测不同方式(MAGE-3、CpG ODN、MAGE-3+CpG ODN 和关抗原对照)致敏DC 对T 淋巴细胞增殖和CTL 对靶细胞BIU-87 的杀伤作用。CpGODN+MAGE-3 抗原肽致敏DC抗裸鼠BIU-87 膀胱癌细胞移植瘤治疗7、11 d 测定移植瘤质量变化,MTT和Western blotting 法分别检测移植瘤细胞的增殖水平及其凋亡蛋白表达的变化。结果:CpG ODN+MAGE-3 抗原肽致敏DC能够促进T淋巴细胞增殖(P<0.05),并显著提高活化T淋巴细胞的CTL对靶细胞BIU-87 的杀伤活性(P<0.05)。体内实验表明,致敏DC治疗7、11 d 的各组移植瘤质量均明显降低(均P<0.05),移植瘤的增殖能力下降也较明显(P<0.05);与其他致敏DC方式相比较,尤以CpG ODN+MAGE-3 致敏DC组在治疗11 d 时的移植瘤质量降低非常显著(P<0.01),且明显促进荷瘤小鼠脾脏单个核细胞的增殖能力(P<0.01);该组在治疗第3 天起移植瘤组织Bcl-2 表达水平明显降低、Bax水平明显升高(均P<0.05 或P<0.01)。结论:CpG ODN能促进MAGE-3 抗原肽致敏DC对膀胱癌BIU-87 细胞的抑制作用,为膀胱癌DC疫苗的临床应用提供了实验依据。
关键词:膀胱癌  BIU-8 细胞  树突状细胞  含CpG序列的细菌寡核苷酸  黑色素瘤抗原基因-3
Inhibitory effects of DC vaccine sensitized with MAGE-3 combined with CpG ODN on bladder cancer BIU-87 cells    Download Fulltext
LI Xiuzhen  XUE Qingjie  LU Hai  NIE Shangdan  WANG Hui  LI Yunqing  ZHAO Longyu  TAN Wenbing
Department of Pathogenic Biology of Jining Medical College, Jining 272000, Shandong, China
Fund Project:Project supported by the National Natural Science Foundation of China (No.31500056), the Science and Technology Foundation of Higher Education of Shandong Province ( No.J11LF03), the Science and Technology Boosting the Old and New Kinetic Energy Conversion Plan of Jining City (No.2017SMNS001),and the Young Teachers Scientific Research Support Fund of Jining Medical College (No.JY2017KJ010)
Abstract:
      Objective: To investigate the role of CpG ODN (CpG oligodeoxynucleotide) adjuvant in enhancing the anti-bladder cancer response induced by MAGE-3 (melanoma antigen gene -3) antigen and its molecular mechanism. Methods: Mononuclear cells were isolated from HLA-A2 type peripheral blood of healthy donors by Ficoll method to prepare mature DC by conventional means. DC surface markers were detected by flow cytometry. MTT assay was used to detect the promotion effect of DCs sensitized by different means (MAGE-3, CpGODN, MAGE-3+CpG ODN, irrelevant control antigen) on the proliferation of T lymphocytes and the killing effect of CTL on BIU-87 tumor cells. The tumor mass of nude mice bearing BIU-87 bladder cell xenograft were examined on Day 7 and 11 after CpG ODN+MAGE-3 sensitized DC treatment. The expression of Bcl-2/Bax protein was detected by Western blotting while the proliferation level of xenograft cells was detected by MTT assay. Results: DCs sensitized by CpG ODN combined with MAGE-3 antigenic peptides could promote the proliferation of T lymphocytes and significantly enhance the killing effect of CTL on target BIU-87 cells (P<0.05). Compared with other sensitized DCs, in vivo experiments showed that 7 and 11 days after treatment, both the tumor volume and weight were significantly reduced (all P<0.05), and the proliferation ability of xenograft tumor was decreased (P<0.05). Compared with other sensitization means, CpG ODN+MAGE-3 especially exhibited obvious inhibitive effect on tumor growth on Day 11, and significantly promoted the proliferation of splenic monocytes of tumor bearing mice (P<0.01); moreover, Bcl-2 expression in xenograft tissues significantly decreased(P<0.01)while Bax expression significantly increased(P<0.05 or P<0.01)on Day 3 after treatment. Conclusion:CpG ODN can promote the inhibitory effect of MAGE-3 sensitized DC on bladder cancer BIU-87 cells, which will provide experimental basis for clinical application of DC vaccine in bladder cancer treatment.
Keywords:bladder cancer  BIU-87 cell  dendritic cell (DC)  CpG oligodeoxynucleotide(CpG ODN)  melanoma antigen gene-3(MAGE-3)
查看全文  查看/发表评论  下载PDF阅读器

Copyright © Biother.Org™ All Rights Reserved; ISSN: 1007-385X  CN 31-1725
主管单位:中国科学技术协会 主办单位:中国免疫学会、中国抗癌学会
地址:上海市杨浦区翔殷路800号 邮政编码:200433 京ICP备13026026号-2

本系统由北京勤云科技发展有限公司设计