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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (7): 19-23.doi: 10.6040/j.issn.1671-7554.0.2014.977

• 基础医学 • 上一篇    下一篇

血管内皮抑素协同肿瘤特异性DC-T细胞的抗肿瘤效应

李星宇, 梁婧, 李岩   

  1. 山东大学附属千佛山医院肿瘤化疗科, 山东 济南 250014
  • 收稿日期:2014-12-21 修回日期:2015-04-28 出版日期:2015-07-10 发布日期:2015-07-10
  • 通讯作者: 李岩。E-mail:liyan16766@163.com E-mail:liyan16766@163.com
  • 基金资助:
    山东省自然科学基金(ZR2010HL015)

Antitumor effect of endostatin synergized with tumor special DC-T cellular therapy

LI Xingyu, LIANG Jing, LI Yan   

  1. Department of Chemotherapy, Cancer Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-12-21 Revised:2015-04-28 Online:2015-07-10 Published:2015-07-10

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摘要： 目的 探讨血管内皮抑素联合肿瘤特异性DC-T细胞对Lewis肺癌小鼠的抗肿瘤效应。方法 建立Lewis肺癌C57BL/6鼠移植瘤模型, 培养小鼠来源肿瘤特异性DC-T细胞, 随机分为A组(PBS对照组)、B组(DC-T组)及C组(DC-T+血管内皮抑素组)。测量小鼠的体质量及肿瘤组织质量和体积, Western blotting检测各组肿瘤组织内血管内皮生长因子(VEGF)和乏氧诱导因子-1α(HIF-1α)蛋白的表达, 流式细胞术检测肿瘤组织细胞悬液内髓源抑制性细胞(MDSC)、肿瘤相关巨噬细胞(TAM, M1/M2)、成熟的树突状细胞(mDC)和CD8+T细胞的比例。结果 与A组比较,B组(P<0.05)、C组(P<0.01)肿瘤生长明显受到抑制;相较于A组, B组VEGF表达下降, 且HIF-1α表达增加(P<0.05), C组VEGF表达明显下降, 且HIF-1α表达明显增加(P<0.01);与A组比较, B组(P<0.05)、C组(P<0.01)的MDSC和M2型TAM比例下降, M1型TAM升高, 肿瘤组织内mDC和CD8+T细胞比例增加。结论 血管内皮抑素联合肿瘤特异性DC-T细胞治疗明显减缓肿瘤生长, 有效逆转了肿瘤微环境的免疫抑制, 从而发挥了协同抗肿瘤效应。

关键词: 细胞免疫治疗, 肿瘤微环境, 血管内皮抑素, 血管新生, 肺肿瘤

Abstract: Objective To investigate the antitumor effect of endostatin combined with tumor special DC-T cellular therapy on lung cancer in Lewis mice. Methods C57BL/6 mice models were established. Tumor antigen special DC-T cells from spleen cells and mice bones were cultured in vitro. The tumor-bearing mice were randomly divided into three groups: A group (PBS control group), B group (DC-T group), and C group (DC-T+endostatin group). The body weight of mice and tumor volume were measured. The VEGF and HIF-1α expressions were determined with Western blotting. The proportions of MDSC, TAM (M1/M2), mDC and CD8+T in suspended tumor cells of tumor tissues were detected with FCM. Results Compared with that in A group, tumor growth in B group (P<0.05) and C group (P<0.01) were inhibited; VEGF expression decreased while HIF-1α expression increased in B group (P<0.05) and C group (P<0.01); the proportions of MDSC and TAM (M2 type) were reduced, while proportions of mDC, TAM (M1 type) and CD8+T cells were elevated in B group (P<0.05) and C group (P<0.01). Conclusion Tumor special DC-T cells combined with endostatin strongly reduce tumor growth, and efficiently reverse the immunosuppression of tumor microenvironment, exhibiting synergistic and much better antitumor effects than monotherapy strategy.

Key words: Cellular therapy, Angiogenesis, Lung neoplasm, Endostatin, Tumor microenvironment

中图分类号: 

  • R73-36+2
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