天津医药

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耐药乳腺癌免疫治疗的实验研究

司玉玲,庞华,綦振家,乔丽葵,王英娟,李世俊   

  1. 天津市第四中心医院
  • 收稿日期:2011-07-22 修回日期:2012-02-03 出版日期:2012-02-15 发布日期:2012-02-15
  • 通讯作者: 庞华

Primary Research of Immunization Therapy on Drug-resistance Breast Cancer Bearing Mice Model (continued)

  • Received:2011-07-22 Revised:2012-02-03 Published:2012-02-15 Online:2012-02-15

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摘要： 目的 我们先前的耐药乳腺癌裸鼠研究表明，负载同种乳腺癌抗原的DC与CIK联合培养后，其荷瘤小鼠的抑瘤效果最强，本实验将进一步针对荷瘤小鼠探究抑瘤效应。 方法 分离健康人外周血获得单个核细胞，分别诱导为树突细胞（DC）和CIK细胞，将人类乳腺癌耐药细胞株MCF-7/ADR细胞的冻融物抗原冲击DC（AP-DC），分别将DC与CIK细胞共培养（AP-DC+CIK 、DC+CIK），将四组细胞（AP-DC+CIK 、DC+CIK、CIK及生理盐水对照）经尾静脉注入裸鼠体内，观察不同组荷瘤标本MDR1表达情况、肿瘤细胞凋亡情况，以及凋亡相关蛋白Bax和Bcl-2表达情况。结果 DC和CIK细胞共孵育，使CIK细胞的杀伤能力提高，其中以AP-DC+CIK组肿瘤凋亡指数最高，MDR1表达最低。四组中，以AP-DC+CIK组Bax表达最高，Bcl-2最低，而NS组相反，Bax表达最低，Bcl-2最高，各组间比较差异均具有统计学意义。结论 经耐药肿瘤抗原负载的DC与CIK共同作用后，其CD4+T细胞数量明显增加，他们可以通过激活Fas/FasL通路，使肿瘤细胞发生凋亡。

关键词: CIK, DC, Bax, Bcl-2, Fas/FasL

Abstract: Objective Our former mice model research showed that after CIK cells were co-cultured with Dendritic cells (DC) loaded with multidrug resistance tumor antigen, the tumor were inhibited most on the same tumor bearing mice model. So we further research into the anti-tumor effect on tumor bearing mice model. Methods DC and CIK were respectively cultured from peripheral blood mononuclear cells (PBMC) derived from healthy individuals. MCF-7/ADR, a kind of breast cancer cell line expressed multidrug resistance, was prepared to obtain the antigen lyses. CIK was co-cultured with DC pulsed or unpulsed by the above antigen lyses (AP-DC+CIK and DC+CIK). So there were AP-DC+CIK, DC+CIK and CIK groups, NS was used as control group. The tumor-bearing mice were injected by intravenous with the above 4 groups’ effector cells. This study researched on the expression of MDR1, the apoptosis of tumor cells and the expression of Bcl-2 and Bax associated with apoptosis. Results After CIK co-cultured with DC, the anti-tumor effect of CIK cells were increased. The AP-DC+CIK group had the highest apoptosis index, and the lowest MDR1 expression. In above 4 groups, the AP-DC+CIK group had the highest Bax and lowest Bcl-2 expression. But the NS group was on the contrary, which meaned the lowest Bax and highest Bcl-2 expression. The difference between each two groups was significance. Conclusion After CIK cells were co-cultured with DC loaded with multidrug resistance tumor antigen, the quantity of CD4+T was increased obviously, which could induce the tumor cells apoptosis through activating Fas/FasL apoptosis pathway.

Key words: CIK, DC, Bax, Bcl-2, Fas/FasL