对小鼠黑色素瘤细胞肺转移抑制作用mGM.docVIP

对小鼠黑色素瘤细胞肺转移抑制作用mGM 　 作者：　田蓉，程绍辉，于继云，李巍，刘玉峰【关键词】 黑色素瘤 Inhibition of lung metastasis of B16 melanoma cells transfected with murine granulocytemacrophage colonystimulating factor in mice 　【Abstract】AIM: To investigate the inhibition of lung metastasis of melanoma by a tumor vaccine of B16 melanoma cells transfected with murine granulocytemacrophage colonystimulating factor (mGMCSF). METHODS: The murine melanoma cell line B16 was transfected with the recombinant plasmid containing mGMCSF. A cell line stably expressing mGMCSF was obtained by G418 selection. The Balb/c mice were administered i.v. with B16 cells transfected with or without mGMCSF respectively and the lung metastasis was examined 2 weeks later. RESULTS: The recombinant cell line B16TR was established after mGMCSF tranfection and the expression of mGMCSF was confirmed by RTPCR. The number of lung metastatic lesions of mice treated with B16TR was significantly fewer than that of mice treated with B16 (n=5, 125.8±34.3 vs 27.8±24.0, Plt;0.01). CONCLUSION: The mGMCSF transfection can significantly suppress the lung metastasis of melanoma in mice. The GMCSF can be a promising adjuvant in the immunotherapy of melanoma. 　　【Keywords】 melanoma; mice; granulocytemacrophage colonystimulating factor; lung neoplasms/secondary; cancer vaccines 　　【摘要】 目的： 探讨小鼠粒细胞巨噬细胞－集落刺激因子（mGMCSF）基因转导对B16黑色素瘤细胞肺转移的抑制效果. 方法： 应用脂质体将含有mGMCSF基因的真核表达载体转染B16小鼠黑色素瘤细胞，经G418加压筛选后，挑选表达mGMCSF基因的B16黑色素瘤细胞. 观察转导或未转导mGMCSF基因的B16黑色素瘤细胞在Balb/c小鼠体内的肺转移. 结果： 转导mGMCSF 基因的B16黑色素瘤细胞可以稳定表达mGMCSF，在小鼠模型上其肺转移灶数目显著少于未转染基因的黑色素瘤细胞对照组，二者差异显著（n=5, 125.8±34.3 vs 27.8±24.0, Plt;0.01）. 结论： mGMCSF转导可显著抑制小鼠黑色素瘤细胞B16的肺转移，提示GMCSF具有治疗黑色素瘤的临床应用前景. 　　【关键词】 黑色素瘤；小鼠；粒细胞巨噬细胞－集落刺激因子；肺肿瘤/继发性；癌症疫苗 　　0引言 　　黑色素瘤是一种恶性程度很高的恶性肿瘤，早期即可发生肺、脑转移. 其发病率有逐渐增高的趋势，然而目前尚无有效的治疗方法［1-3］. 近年来，免疫治疗已经成为黑色素瘤治疗研究的一个热点［2,4-5］，其中，联合细胞因子的肿瘤细胞免疫是一个重要的方向，可以涉及几乎全部与免疫系统相关的细胞因子. GMCSF具有可增强粒细胞、巨噬细胞活性，增强MHCⅠ, MHCⅡ, B7分子的表达，增强抗原提呈功能等广泛的生物学活性，因而可能在肿瘤的免疫治疗中具有着重要作用. 我们拟将GMCSF基因转染黑色素瘤细胞系B16，观察其对黑色素瘤细胞生长及转移的影响，为抗黑素瘤免疫治疗