NTSR1基因对胃腺癌细胞增殖和侵袭的影响及机制
DOI: 10.3971/j.issn.1000-8578.2018.17.0658
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Abstract:
摘要 目的 探讨NTSR1基因在胃癌细胞增殖侵袭中的作用及其可能的机制。方法 应用免疫组织化学Envision二步法检测分析233例胃癌组织中NTSR1蛋白表达与EGFR及HER2的关系。检测胃癌细胞株NTSR1 mRNA表达，选取表达丰度较高的细胞株作为实验对象。构建干扰效率最高的shNTSR1 MKN-45细胞稳定株。采用MTT及细胞侵袭实验检测NTSR1基因沉默对胃癌细胞增殖及侵袭能力的影响。检测shNTSR1对Cancer Phenotype信号通路中19种相关基因表达的影响。结果 （1）233例胃癌NTSR1阳性表达与EGFR及HER2表达均存在显著正相关性（P<0.05），同时EGFR与HER2两者表达亦存在显著正相关性（P<0.05）。（2）NTSR1在MKN-45中的表达丰度较高。（3）成功构建NTSR1 shRNA表达载体。（4）经NTSR1 shRNA干扰，MKN-45的细胞增殖倍数明显下调（P<0.05）。（5）经NTSR1 shRNA干扰，MKN-45的侵袭转移率显著减少（P<0.05）。（6）经shRNA干扰NTSR1表达后， MKN-45细胞的Cancer Phenotype信号通路相关基因中的p27Kip1蛋白的表达水平显著上调，同时，EGFR、HER2、EpCAM及Met也呈现较明显的下调趋势。结论 NTSR1在胃癌的发生发展中起重要作用，其可能通过多维度调控EGFR/HER2信号及p27Kip1、EpCAM、Met等Cancer Phenotype信号通路相关基因来促进胃癌细胞的增殖、侵袭及转移
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