中国肿瘤生物治疗杂志2018，Vol.25Issue(1)：56-61,6.DOI:10.3872/j.issn.1007-385x.2018.01.010
粒细胞-巨噬细胞集落刺激因子对结肠癌肝转移的促进作用及其可能机制
Promoting effect of granulocyte-macrophage colony stimulating factor on liver metastasis of colon cancer and its underlying mechanisms
摘要
Abstract
Objective:To investigate the effect of granulocyte-macrophage colony stimulating factor(GM-CSF) on liver metastasis of colon cancer and the underlying mechanisms.Methods:GM-CSF gene and shRNA targeting GM-CSF were stably transfected into human colon cancer HCT116 and SW480 cell lines,respectively;the expression of GM-CSF was detected by ELISA.Liver metastasis model of colon cancer was established by injecting cancer cells into spleen.Some of the model mice were intraperitoneally injected with recombinant human GM-CSF every other day (3 μtg,0.6 μg/mice).Four weeks after model establishment,liver gross and tumor metastasis were observed.The expression of N-cadherin and matrix metalloproteinase 2 (MMP2) was detected by Real-time fluorescent quantitative PCR while E-cadherin was detected by Western blotting.Results:According the expression of GM-CSF,HCT116 cells were grouped into low,median and high expression subgroups (GMlo,GMint,GMhiHCT 116);Meanwhile,GMKDSW480 group (GM-CSF knockdown) was established.Liver gross and pathological results showed that injecting of GM-CSF-overexpressed HCT 116 cells or exogenous GM-CSF remarkably increased the amounts of liver metastasis;In contrast,knockdown of GM-CSF showed the opposite effect.Furthermore,GM-CSF over-expression significantly up-regulated the levels of N-cadherin and MMP2 as well as down-regulated the levels of E-cadherin (P＜0.05).Conclusion:GM-CSF can potently promote liver metastasis of colon cancer xenograft,which maybe due to the down-regulation of E-cadherin and up-regulation of N-cadherin and MMP2.关键词
粒细胞-巨噬细胞集落因子/结肠癌/肝转移/上皮钙黏素/神经钙黏素/基质金属蛋白酶2Key words
granulocyte-macrophage colony stimulating factor (GM-CSF)/colon cancer/liver metastasis/E-cadherin/N-cadherin/matrix metalloproteinase 2(MMP2)分类
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丁欣,沈倍奋,陈国江,吕忠霖,许可,侯春梅,肖鹤,王仁喜,韩根成,冯健男,黎燕..粒细胞-巨噬细胞集落刺激因子对结肠癌肝转移的促进作用及其可能机制[J].中国肿瘤生物治疗杂志,2018,25(1):56-61,6.基金项目
国家重点基础研究发展计划(973)项目(No.2015CB553704) （973）
国家自然科学基金资助项目(No.81672803,81472647).Project supported by the State Key Development Program for Basic Research of China (No.2015CB553704),and the National Natural Science Foundation of China (No.81672803,81472647) （No.81672803,81472647）
