›› 2011, Vol. 23 ›› Issue (5): 353-356.doi: 10.3969/j.issn.1004-616x.2011.05.007

• 论著 • 上一篇    下一篇

CIK细胞体内外抗宫颈癌HeLa细胞活性的研究

刘爱民,霍红旗,李 鹏*,张 灿,王海东   

  1. 河北省邯郸市中心医院,河北 邯郸 056001
  • 收稿日期:2011-01-18 修回日期:2011-03-17 出版日期:2011-09-30 发布日期:2011-09-30
  • 通讯作者: 李 鹏

Antitumor effects of cytokine-induced killer cells on cervical cancer HeLa cells in vitro and in vivo

LIU Ai-min,HUO Hong-qi,LI Peng*,ZHANG Can,WANG Hai-dong   

  1. The Central Hospital of Handan City, Handan 056001, Hebei, China
  • Received:2011-01-18 Revised:2011-03-17 Online:2011-09-30 Published:2011-09-30
  • Contact: LI Peng

摘要: 目的: 探讨细胞因子诱导的杀伤(cytokine-induced killer,CIK)细胞的体内外抗宫颈癌HeLa细胞活性。方法:收集8名健康献血者和8名宫颈癌患者的新鲜外周血,分别通过常规方法分离外周血单核细胞(peripheral blood mononuclear cells,PBMC),应用相应细胞因子体外诱导分化出CIK细胞,动态观察CIK细胞的体外增殖活性、细胞表型和对HeLa细胞的杀伤活性;在BALB/c裸鼠皮下接种效应细胞,观察宫颈癌患者CIK细胞对接种HeLa细胞的荷瘤鼠的抑瘤作用,同时设淋巴因子激活的杀伤细胞 (lymphokine activated killer cells,LAK)和PBMC细胞作为对照。结果:源于健康人和宫颈癌患者的CIK细胞间的增殖活性无明显区别(P >0.05)。表型分析结果表明,两种来源的CIK细胞中CD3+CD56+ 双阳性细胞均得到了大量扩增,宫颈癌患者CIK细胞中CD3+CD56+ 双阳性细胞在实验开始前约占0.13%,到实验后第28天上升到25.8%。体外实验表明,宫颈癌患者的CIK细胞杀伤宫颈癌HeLa细胞的细胞毒活性明显高于PBMC细胞。裸鼠体内实验表明,宫颈癌患者CIK细胞能够显著抑制肿瘤的生长,其抑瘤率可达80.6%,高于LAK细胞的59.1%和PBMC细胞的38.3% (P<0.01)。CIK治疗后肿瘤体积明显比空白对照组缩小 (P<0.05)。结论:宫颈癌患者CIK细胞具有较强的体内外抗宫颈癌细胞活性,有可能用于临床上宫颈癌的过继性免疫治疗。

关键词: CIK细胞, 宫颈癌, 抗肿瘤, 过继性免疫治疗

Abstract: OBJECTIVE: To explore the differences of cytokine-induced killer (CIK) cells from healthy persons and patients with primary cervical cancer,in their phenotype,proliferation activity,cytotoxic activity and antitumor effects in vitro and in vivo. METHODS:CIK cells were generated by IFN-γ,CD3McAb,IL-2,IL-1 induction of cultured peripheral blood mononuclear cells (PBMC) of both 8 healthy blood donors and 8 cervical cancer patients. These treated cells were followed at different intervals by MTT assays and flow cytometry analysis. The antitumor activity of the CIK,LAK and PBMC cells were evaluated in BALB/c nude mice bearing HeLa cervical cancer. RESULTS:There was no significant difference in proliferation performance of CIK cells between healthy persons and cervical cancer patients (P>0.05). The flow cytometry analysis showed that the percentage of CD3+CD56+ cells increased from 0.13% on day 0 to 25.8% on day 28. CIK cells generated from patients with cervical cancer patients possessed a higher antitumor cytotoxic activity in vitro than PBMC. In addition,CIK cells had a stronger suppressive effect on tumor growth in BALB/c nude mice bearing cervical cancer than LAK cells (median inhibitory rates 80.6% vs 59.1%, respectively,P <0.01) or PBMC (median inhibitory rates 80.6% vs 38.3%,respectively,P <0.01). The tumor size in the experiment group was smaller than that in the control group after CIK treatment (P<0.05). CONCLUSION:CIK cells had a significantly stronger suppression on growth of cervical cancer cells,providing an experimental basis for CIK clinical use as an adoptive immunotherapy.

Key words: cytokine induced killer cell, cervical cancer, antitumor, adoptive immunotherapy