| 莫文秀,孙立新,王佳佳.肿瘤干细胞多靶点联合治疗效果分析[J].中国肿瘤,2014,23(2):162-169. |
| 肿瘤干细胞多靶点联合治疗效果分析 |
| The Efficacy of Combined Multi?鄄targeted Cancer Stem Cell Therapy |
| 投稿时间：2013-10-13 |
| DOI：10.11735/j.issn.1004-0242.2014.02.A017 |
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| 中文关键词: 肿瘤干细胞 单克隆抗体 联合 多靶点 9A9 15D2 |
| 英文关键词:cancer stem cell monoclonal antibody combination multi?鄄targeted 9A9 15D2 |
| 基金项目:国家科技重大专项（2011ZX09102-010） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨有效的肿瘤生物治疗新思路，用肝癌细胞系Bel7402-V3为细胞模型检测联合单克隆抗体9A9和15D2对其干性功能（自我更新、侵袭和耐药）的影响。［方法］ 采用活细胞流式免疫荧光术检测单独抗体、联合抗体与肿瘤干细胞标志物ESA在Bel7402-V3亲本及sphere细胞中的表达；甲基纤维素成球实验和Transwell小室侵袭实验分别检测抗体对Bel7402-V3亲本细胞成球能力和侵袭能力的影响；CCK8法及IC50法检测联合抗体对Bel7402-V3亲本细胞耐药能力的影响。［结果］ 流式荧光结果显示：标志物ESA、单抗15D2、单抗9A9所识别的细胞比例在Bel7402-V3 sphere细胞中比在亲本细胞中分别富集了2.6倍、4.1倍、2.0倍；在Bel7402-V3亲本和sphere细胞中，联合单抗与标志物共染比例（9A9+15D2与ESA）大于单抗分别与标志物共染比例之和［（9A9+ESA）+（15D2+ESA）］；单抗9A9与15D2联合时对Bel7402-V3亲本细胞的成球抑制率和侵袭抑制率均明显高于等浓度的单种单抗对Bel7402-V3亲本细胞的功能抑制；经联合单抗处理的Bel7402-V3亲本细胞耐药能力较经等浓度单种单抗处理的细胞耐药能力显著降低［9A9+15D2：IC50为0.32μg/ml，9A9：IC50为0.58μg/ml，15D2：IC50为0.56μg/ml。［结论］ 肿瘤干细胞中存在不同亚群，其在不同的信号通路或基因水平上发挥了不同的作用。联合多靶点的抗体治疗能显著提高疗效。 |
| 英文摘要: |
| Abstract：［Purpose］To investigate the silver lining of cancer biological-therapeutic regimen.The hepatic carcinoma cell line Bel7402-V3 intervened with combination of monoclonal antibodies 15D2 and 9A9 to monitor its subsequent functions change including self-renewal，invading and drug-resistance abilities. ［Methods］Hepatic carcinoma cell line Bel7402-V3 was choose as an ideal model，in which living cell flow cytometry was adopted to identify the expression of sole antibody，combination antibodies and cancer stem cell marker among parent cells and spheres. Antibodies's influence on cell self-renewal，invade ability and drug-resistance were examined by methyl cellulose spheres，Transwell invading test and CCK8 plus IC50 method respectively.［Results］ The proportion of cells identified by cancer stem cell marker ESA，9A9A and 15D2 in the sphere cells were enriched 2.6 times，2.0 times and 4.1 times more than those in the parental cells，respectively. The co-expression antigen of combined antibodies and ESA was more than the sum of antigen located on (9A9+ESA) and (15D2+ESA).The combined antibodies have notable inhibitory ratio than sole antibody with equal concentration on spheres forming and invading ability，which is same as drug-resistance. The IC50 in combined antibodies group，9A9 and 15D2 was 0.32μg/ml，0.58μg/ml and 0.56μg/ml，respectively.［Conclusion］There are different kinds of sub-sets in cancer stem cells bearing distinct functions on many signal pathways and gene expression. Combined multi-targeted antibodies are capable of increasing efficacy of treatment. |
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