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单基因和双基因联合治疗对小鼠B16-F10黑色素瘤生长抑制作用研究
Inhibitory Effect of Single Gene and Double Gene Combined Therapy Drugs on the Growth of B16-F10 Melanoma in Mice
韦世元1, 唐放1, 彭旭2, 何学令2, 尹海林2*
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DOI:10.11984/j.issn.1000-7083.20190170
作者单位:1. 四川大学生命科学学院, 成都 610065;
2. 四川大学实验动物中心, 成都 610041
中文关键字:B16-F10黑色素瘤;粒细胞-巨噬细胞集落刺激因子;血管内皮生长因子;基因治疗
英文关键字:B16-F10 melanoma; granulocyte-macrophage colony-stimulating factor; vascular endothelial growth factor; gene therapy
中文摘要:目的 研究阳离子脂质体介导mGM-csf和mFlt-kdr3基因治疗以及2个基因联合治疗对小鼠B16-F10黑色素瘤肺转移以及实体瘤的生长抑制作用。方法 通过尾静脉注射法和皮下注射法分别将105个以及106个对数生长期黑色素瘤细胞注入BALB/c小鼠体内,构建小鼠肺转移模型和腋下实体瘤模型。将2组模型小鼠分别分成5组:mFlt-kdr3治疗组、mGM-csf治疗组、联合治疗组(1次mFlt-kdr3,2次mGM-csf)、H1299脂质体质粒对照组和生理盐水对照组。肺转移模型小鼠建模3周后,尾静脉给药治疗,每次给药80 μL,每次间隔1 d,共3次。完成后3 d,解剖取出小鼠肺组织并对肿瘤灶进行计数、苏木精-伊红染色。实体瘤模型小鼠在建模1周后开始瘤体穿刺给药,每次给药25 μL,每次间隔1 d,共9次,每次给药前用游标卡尺测量瘤体的长、短径。结果 肺转移治疗实验中,治疗组平均肿瘤个数显著少于对照组(P<0.05),且联合治疗组肿瘤个数最少,并且肺部结构完整,基本未见明显的肿瘤灶,可以看到明显的肺泡结构。实体瘤模型实验中,治疗组瘤体平均体积显著小于对照组(P<0.05),且在观察的时间内联合治疗组瘤体平均体积呈现明显的下降趋势,治疗组的疗效价值为联合治疗组 > mFlt-kdr3治疗组 > mGM-csf治疗组。结论 GM-csf和Flt-kdr3基因药物对黑色素瘤具有协同治疗效用,可以明显抑制肺部肿瘤灶的形成和实体瘤的生长。
英文摘要:Objective To study the effect of cationic liposome-mediated mGM-csf and mFlt-kdr3 gene therapy and combined gene therapy on lung metastasis and tumor growth inhibition of mouse B16-F10 melanoma.Methods The lung metastasis model and subcutaneous solid tumor model were established by injecting 105and 106 melanoma cells into BALB/c mice by caudal vein injection and subcutaneous injection, respectively. The mice of the 2 groups were divided into 5 subgroups: mFlt-kdr3 group, mGM-csf group, combined treatment group (1 mFlt-kdr3, 2 mGM-csf), empty vector plasmid group, and normal saline control group. After the model was established for 3 weeks, the mice with pulmonary metastasis began to be treated by intravenous injection of drugs (80 μL per time, 1 day interval, a total of 3 times). After 3 days, the lung tissue was dissected and the tumor foci were counted, and HE staining was performed. The solid tumor mouse models were treated with tumor puncture administration for one week (25 μL per dose, 1 day interval, a total of 9 times). In the meantime, the length of mouse tumor were measured with vernier caliper before each administration.Results The average number of tumor in the treatment group was much lower than that in the control group (P<0.05). The number of tumor in the combined treatment group was the least, and the lung structure was intact. Obvious alveolar structure can be observed by HE staining. In the solid tumor model test, the average tumor volume in the treatment group was much lower than that in the control group (P<0.05), and the average tumor volume in the combined treatment group was the most obvious during the experiment. The combined treatment group had the highest therapeutic effect, followed by mFlt-kdr3 group and mGM-csf group.Conclusion GM-csf and Flt-kdr3 gene therapeutic drugs have synergistic effect on melanoma, which can inhibit the formation of lung tumor focus and the growth of solid tumor.
2020,39(1): 34-40 收稿日期:2019-05-16
分类号:Q95-33;R979.1
作者简介:韦世元(1994-),硕士研究生,主要从事实验动物相关研究,E-mail:979543310@qq.com
*通信作者:尹海林,E-mail:13183830576@163.com
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