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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2013, Vol. 07 ›› Issue (04) : 298 -302. doi: 10.3877/cma.j.issn.1674-0793.2013.04.013

所属专题： 文献；

论著

β-葡萄糖神经酰胺与HBsAg-DC瘤苗协同治疗肝癌的实验研究
戴强生1, 李鹤平2,†(), 龙健婷1, 曾睿芳1, 张冰2, 周波2, 幸思忠3, 曾志荣4, 陈伟2, 杨建勇2   
  1. 1. 510080　中山大学附属第一医院肿瘤科
    2. 510080　中山大学附属第一医院放射介入科
    3. 深圳市宝安人民医院内科
    4. 510080　中山大学附属第一医院内科
  • 收稿日期:2013-04-27 出版日期:2013-08-01
  • 通信作者: 李鹤平
  • 基金资助:
    国家自然科学基金项目(30600156，81071247); 广东省科技计划项目(2011B031800022)

Experimental study of β-GC combined with HBsAg gene-modified dendritic cell-based tumor vaccine to hepatocellular carcinoma by different immune ways

Qiang-sheng DAI1, He-ping LI2,†(), Jian-ting LONG1, Rui-fang ZENG1, Bing ZHANG2, Bo ZHOU2, Si-zhong XING3, Zhi-rong ZENG4, Wei CHEN2, Jian-yong YANG2   

  1. 1. Department of Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080 , China
  • Received:2013-04-27 Published:2013-08-01
  • Corresponding author: He-ping LI
  • About author:
    Corresponding author: LI He-ping, Email:
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戴强生, 李鹤平, 龙健婷, 曾睿芳, 张冰, 周波, 幸思忠, 曾志荣, 陈伟, 杨建勇. β-葡萄糖神经酰胺与HBsAg-DC瘤苗协同治疗肝癌的实验研究[J]. 中华普通外科学文献(电子版), 2013, 07(04): 298-302.

Qiang-sheng DAI, He-ping LI, Jian-ting LONG, Rui-fang ZENG, Bing ZHANG, Bo ZHOU, Si-zhong XING, Zhi-rong ZENG, Wei CHEN, Jian-yong YANG. Experimental study of β-GC combined with HBsAg gene-modified dendritic cell-based tumor vaccine to hepatocellular carcinoma by different immune ways[J]. Chinese Archives of General Surgery(Electronic Edition), 2013, 07(04): 298-302.

目的

探讨β-葡萄糖神经酰胺（β-GC）联合乙型肝炎表面抗原（HBsAg）基因修饰树突状细胞（dendritic cell, DC）瘤苗治疗肝癌的作用。

方法

以重组腺病毒为载体构建HBsAg-DC瘤苗。将C57BL/6J小鼠随机分为6组（A-F，6只/组），其中A、B、C组接种PBS液2次，D、E、F组接种HBsAg-DC瘤苗2次。皮下注入HepG2 22.1.5肝癌细胞当天始，B、E组接受β-GC（1.5 μg）腹腔注射，C、F组接受β-GC（15 μg）灌胃给药，A、D组为安慰剂对照，比较不同组间移植瘤生长情况。

结果

B、C组移植瘤生长较之A组明显受抑（P<0.05），E、F组移植瘤生长较之D组明显受抑（P<0.05）。A-F组移植瘤大小（mm3）分别为364.2±3.06，236.5±8.96，251.0±5.76，75.0±5.9，35.3±4.46，38.5±5.47。经腹腔注射给药与灌胃给药相比在抗瘤作用方面差异无统计学意义。

结论

β-GC经腹腔或灌胃给药均具有提高HBsAg-DC瘤苗的免疫治疗作用，其协同抗肿瘤效应的机制可能通过激活NKT细胞。

关键词: 树突状细胞, HBs-Ag基因, HepG2 22.1.5肝癌细胞, 瘤苗, 基因疗法, β-葡萄糖神经酰胺
Objective

To explore the efficacy of β-GC combined with HBsAg gene-modified DC vaccine on animal model with HCC using different immunization routes.

Methods

Recombinant adenovirus vector-mediated HBsAg gene-modified DC was used to construct HBsAg-DC which was infused into C57BL/6J mice bearing HBsAg-related HCC by subcutaneous injection. Mice in group A, B and C were vaccinated with PBS, group D, E and F were vaccinated with pAd-HBsAg-DC twice before HepG2 22.1.5 inoculation as described above. Starting at the day of inoculation, mice were treated with daily intra-peritoneal. (ip, 1.5μg per mouse) β-GC injection in group B and E or daily oral β-GC doses(po, 15μg per mouse) in group C and F. Group A and D receiving vehicle (po) were set as control for β-GC treatment.The effectiveness of the immune therapy on tumor growth was compared among different groups.

Results

Tumor size measured 36 days after inoculation was (364.2±3.06)mm3 in group A, (236.5±8.96)mm3 in group B, (251.0±5.76)mm3 in group C, (75.0±5.9)mm3 in group D, (35.3±4.46)mm3 in group E, and (38.5±5.47)mm3 in group F. The application of β-GC demonstrated anti-tumor activity by itself (group B and C), and also enhanced the tumor preventive effect of pAd-HBsAg-DC (group E and F). No difference in tumor growth was observed between ip and po application of β-GC.

Conclusion

β-GC may serve as an immune enhancer to augment the anti-tumor immunity triggered by HBsAg gene-modified DC vaccine. It's antitumor effect may be related to activation of NKT cells.

Key words: Dendritic cells (DC), HBs-Ag gene, HepG2 22.1.5 hepatoma cells, Vaccine, Gene therapy, β-GC
图1 光学显微镜下DC形态特征（×400）
图2 DC表型标志物免疫荧光法检测
图3 DC刺激同种异体T淋巴细胞的增殖能力
图4 β-GC激活肝NKT细胞及与HBsAg-DC瘤苗协同抗癌的效能
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