Li Qi-Ying, Shi Yang, Huang De-Hong, Yang Tao, Wang Jiang-Hong, Yan Guo-He, Wang Hong-Yu, Tang Xian-Jun, Xiao Chun-Yan, Zhang Wen-Jun, Zhang Man, Wang Li, Gong Yi, Yang Wei, Wu Xian-Yu, Xiang Ying
Department of Biotherapy and Hemo-Oncology, Chongqing Cancer Institute 181 Hanyu Road, Chongqing 400030, China.
Center of Endoscopy Examination & Therapy, Chongqing Cancer Institute 181 Hanyu Road, Chongqing 400030, China.
Int J Clin Exp Med. 2015 Apr 15;8(4):5601-10. eCollection 2015.
To investigate the prognosis of advanced liver cancer patients treated with CIK-DCs and the mechanism of apoptosis of HEPG 2 cells.
67 patients were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were separated, of which adherent PBMCs used granulocyte 2 macrophage colony2 stimulating factor (GM2CSF), tumor necrosis factor 2α (TNF2α), and interleukin 24 (IL24) to induce DCs, which were sensitized with antigen of autologous or exogenous cancer cells to obtain Ag-DCs; suspended PBMCs used interferon 2γ (IFN2γ), IL-2, and CD 3 monoclonal antibody (CD3mAb) respectively, to induce CIK cells. DCs and CIK cells were cultured together. Flow cytometry was used to detect the phenotypes of DCs and CIK cells, and the blood retransfused into patients. Western blot and flow cytometer were used to analyze the growth cycle of HepG 2 cells and the expression of BAX and PCNA.
No patients underwent complete remission, 5 obtained partial remission and 29 had stable disease. Of the 31 patients whose lesions could not be evaluated, 17 received effective treatment, showing that the immune response was enhanced. In vitro laboratory experiments revealed that DC-CIK cells markedly affected the growth cycle of HepG 2 cells. Analysis showed that DC-CIK cells enhanced the gene expression of BAX and inhibited the activity of PCNA.
Co-cultured DCs and CIK cells inhibit the proliferation and migration of liver cancer cells by down-regulating PCNA and up-regulating BAX. This approach may be an effective method to treat advanced liver cancer.
探讨细胞因子诱导的杀伤细胞(CIK)与树突状细胞(DC)联合治疗晚期肝癌患者的预后及人肝癌细胞系(HEPG 2)细胞凋亡机制。
67例患者纳入本研究。分离外周血单个核细胞(PBMC),其中贴壁PBMC用粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α(TNF-α)和白细胞介素-4(IL-4)诱导DC,用自体或外源性癌细胞抗原致敏获得抗原负载的DC(Ag-DC);悬浮PBMC分别用干扰素-γ(IFN-γ)、IL-2和CD 3单克隆抗体(CD3mAb)诱导CIK细胞。DC和CIK细胞共培养。采用流式细胞术检测DC和CIK细胞表型,并回输给患者。采用蛋白质免疫印迹法和流式细胞仪分析HepG 2细胞生长周期及BAX和增殖细胞核抗原(PCNA)表达。
无患者完全缓解,5例部分缓解,29例病情稳定。31例无法评估病变的患者中,17例接受有效治疗,提示免疫反应增强。体外实验显示,DC-CIK细胞显著影响HepG 2细胞生长周期。分析表明,DC-CIK细胞增强BAX基因表达并抑制PCNA活性。
DC与CIK细胞共培养通过下调PCNA和上调BAX抑制肝癌细胞增殖和迁移。该方法可能是治疗晚期肝癌的有效方法。