陈 心,伍 龙,褚玉新.肿瘤干细胞-DC疫苗联合白介素-2治疗小鼠恶性黑色素瘤的研究[J].肿瘤学杂志,2017,23(11):955-958. |
肿瘤干细胞-DC疫苗联合白介素-2治疗小鼠恶性黑色素瘤的研究 |
Cancer Stem Cells-DC Vaccine Combined with Interleukin-2 in Treatment of Malignant Melanoma in Mice |
投稿时间:2017-09-13 |
DOI:10.11735/j.issn.1671-170X.2017.11.B004 |
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中文关键词: 恶性黑色素瘤 肿瘤干细胞 树突状细胞 疫苗 |
英文关键词:words:cancer stem cells malignant melanoma dendritic cell vaccine |
基金项目:国家自然科学基金资助项目(81302133,81670123);中央高校基本科研业务费专项基金资助项目(2042014kf0149) |
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中文摘要: |
摘 要:[目的] 研究荷载肿瘤干细胞(CSCs)抗原的树突状细胞疫苗联合白介素-2(IL-2)治疗小鼠恶性黑色素瘤的研究。[方法] 利用Aldefluor染料从小鼠恶性黑色素瘤细胞系D5中分选出肿瘤干细胞,将CSCs制备成细胞裂解液加载在DC细胞上制备成CSCs-DC疫苗。将D5细胞接种至C57BL/6小鼠皮下建立小鼠恶性黑色素瘤模型,随机分成磷酸盐缓冲液组 (PBS)、白介素-2组(IL-2)、CSCs-DC疫苗组(CSCs-DC)、CSCs-DC疫苗联合白介素-2组(CSCs-DC+ IL-2),并给予相应的治疗。测量并记录各组肿瘤大小变化和小鼠生存期,实验终点取小鼠脾脏,体外培养激活后利用ELISA法测定B细胞分泌IgG水平,LDH细胞毒性实验测定细胞毒性淋巴细胞(CTL)活性。 [结果] CSCs-DC+IL-2组肿瘤生长明显慢于PBS组,IL-2组及CSCs-DC组(P<0.05)。小鼠生存期CSCs-DC+IL-2组最长为58.33±1.67天,CSCs-DC组为51.67±0.33天,较IL-2组43.33±2.40天长,PBS组平均生存时间最短,为34.00±1.53天。CSCs-DC+IL-2组小鼠脾脏中B细胞分泌IgG水平和CTL活性最高,CSCs-DC组次之,IL-2组较CSCs-DC组和CSCs-DC+IL-2组低,但较PBS组高,差异有统计学意义(P<0.01)。[结论]CSCs-DC疫苗联合IL-2方案在治疗恶性黑色素瘤的小鼠模型中效果较CSCs-DC疫苗组和IL-2组好,与IL-2提高T/B细胞活性有关。 |
英文摘要: |
Abstract:[Objective] To study the therapeutic effect and mechanism of cancer-stem-cells-antigen-loaded dendritic cell vaccine combined with interleukin-2 in treating mouse malignant melanoma. [Methods] CSCs were sorted out from malignant melanoma cell lines(D5) using Aldefluor. bone-marrow derived DCs were pulsed with CSCs lysate to generate CSCs-DC vaccine. The C57BL/6 mice were challenged with subcutaneous injection of heterogeneous D5 tumor cells. The mice having tumor were divided into four groups:PBS,interleukin-2 (IL-2),CSCs-DC vaccine(CSCs-DC),and CSCs-DC vaccine+IL-2 (CSCs-DC+ IL-2). Tumor size was measured,and survival was monitored and recorded as the percentage of survivors after tumor inoculation. At the end of the experiment,spleens in mice were harvested,cultured,and activated. IgG levels secreted by B cells were measured using ELISA,the cytotoxic lymphocyte(CTL) activity was measured using LDH cytotoxicity assay. [Results] The tumor size in the CSCs-DC+ IL-2 group was significantly smaller than those in the PBS group,the IL-2 group,and the CSCs-DC group(P<0.05). The average survival time of the CSCs-DC+ IL-2 group(58.33±1.67d) was the longest among the four groups and that of the PBS group(34.00±1.53d) was the shortest;and the average survival time of the CSCs-DC(51.67±0.33d) group was longer than that of the IL-2 group(43.33±2.40d). Levels of IgG secreted by B cell and CTL activity in mice spleen were the highest in the CSCs-DC+ IL-2 group,followed by the CSCs-DC group,IL-2 group,and the PBS group. These differences were statistically significant (all P<0.01). [Conclusion] CSCs-DC vaccine combined with IL-2 in treating mouse malignant melanoma is more effective than IL-2 treatment and CSCs-DC vaccine used alone. |
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