Zhao Jing-Jing, Pan Ke, Wang Qi-Jing, Xu Zheng-Di, Weng De-Sheng, Li Jian-Jun, Li Yong-Qiang, Xia Jian-Chuan
State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.
Chin J Cancer. 2013 Oct;32(10):553-60. doi: 10.5732/cjc.012.10249. Epub 2013 Mar 8.
Chuankezhi (CKZ), a new Chinese medicine, plays an important role in immunoregulation. Cytokine-induced killer (CIK) cells have been commonly used for immunotherapy in recent years. In this study, we aimed to investigate the immunoregulatory effect of CKZ on CIK cells. Peripheral blood monocytes were isolated from healthy donors, and CIK cells were generated by culturing monocytes with interferon-gamma (IFN-γ) and interleukin 2. Different concentrations of CKZ were added on day 2. After incubation for 14 days in culture, the antitumor effects of CIK cells were measured by cytotoxicity assay. Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype, intracellular cytokine production, and apoptosis. The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated. CKZ increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. CKZ-conditioned CIK cells showed a greater ability to kill tumor cells, as well as a higher frequency of IFN-γ and TNF-α production, compared with the CIK cells in the control group. CKZ also suppressed the apoptosis of CIK cells in vitro. Furthermore, CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK, CKZ, or normal saline control groups. Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.
喘可治(CKZ)是一种新型中药,在免疫调节中发挥着重要作用。细胞因子诱导的杀伤(CIK)细胞近年来已普遍用于免疫治疗。在本研究中,我们旨在探讨CKZ对CIK细胞的免疫调节作用。从健康供体中分离外周血单核细胞,并用干扰素-γ(IFN-γ)和白细胞介素2培养单核细胞以生成CIK细胞。在第2天加入不同浓度的CKZ。培养14天后,通过细胞毒性试验测定CIK细胞的抗肿瘤作用。采用流式细胞术探讨CKZ对CIK细胞免疫表型、细胞内细胞因子产生及凋亡的影响。还研究了CKZ对裸鼠中CIK细胞抗肿瘤活性的影响。CKZ增加了CD3+CD56+ CIK细胞的百分比,但未显著改变CD4+、CD8+或CD4+CD25+ CIK细胞的百分比。与对照组的CIK细胞相比,经CKZ处理的CIK细胞表现出更强的杀伤肿瘤细胞的能力,以及更高频率的IFN-γ和TNF-α产生。CKZ在体外也抑制了CIK细胞的凋亡。此外,与CIK、CKZ或生理盐水对照组相比,CKZ联合CIK细胞在体内对肿瘤生长具有更强的抑制作用。我们的结果表明,CKZ增强了CIK细胞的抗肿瘤活性,是一种潜在的肿瘤免疫治疗药物。