HOXC10对胃癌细胞增殖和转移的调控作用及其机制研究

The effects and mechanisms of HOXC10 on gastric cancer cell proliferation and metastasis

目的观察H OXC10对胃癌细胞增殖和转移的调节作用。方法采用RT-PCR方法检测人胃癌组织及癌旁正常组织中HOXC10的mRNA水平,同时检测胃癌细胞株BGG823.SGC7901细胞和正常胃黏膜细胞株GES-1细胞中HOXClOmRNA和蛋白的表达。将胃癌BGC823细胞分别进行HOXCIO siRNA、阴性对照siRNA转染,并采用CCK-8法观察各组细胞增殖能力,采用细胞克隆形成检测各组细胞的克隆形成能力,采用transweU小室实验观察各组细胞侵袭能力,采用蛋白质印迹法实验检测上皮间质表型蛋白的表达。采用裸鼠皮下移植瘤和肺转移模型评价HOXCIO对BGC823肿瘤生长和肺转移能力的影响。结果人胃癌组织中HOXC10的表达水平高于癌旁正常组织(PV0.05);BGC823.SGC7901细胞HOXCIO表达水平均高于GES-1细胞(P<0.05)oBGC823细胞HOXCIO siRNA组的细胞增殖能力,克隆形成能力和侵袭能力均显著低于siRNA对照序列组(均P<0.05);与NC siRNA组相比,HOXCIO siRNA组的间质表型蛋白波形蛋白(vimentin)和转移相关分子MMP-9的mRNA和蛋白均显著下调,而上皮表型蛋白上皮钙黏素的mRNA和蛋白均显著上调。HOXCIO过表达引起的细胞功能、mRNA和蛋白的变化与HOXCIO siRNA相反。HOXCIO siRNA能显著抑制BGC823细胞裸鼠移植瘤的生长和肺转移灶的形成。结论HOXCIO是人胃癌中潜在的诊断和预后生物标志物或治疗靶点。

Objective To investigate the expression of HOXC10 in gastric cancer cells and its effects on cell proliferation and metastasis. Method The HOXC10 m RNA levels in human gastric cancer tissues and tumor adjacent normal tissues were detected by RT-PCR assay. The m RNA and protein levels of HOXC10 in human gastric cancer cell lines BGC823, SGC7901 and human normal gastric mucosa epithelial cells GES-1 were measured by RT-PCR and Western blot analysis. Human gastric cancer cell BGC823 were transfected with HOXC10 si RNA and NC si RNA, then subjected to proliferation, colony formation and invasion function studies via CCK-8, cell clone formation and transwell invasion assay, respectively. Western blot assay was used to determine the changes of EMT proteins in BGC823 cells after HOXC10 si RNA transfection. Nude mice xenografts and lung metastasis models were used to test the effects of HOXC10 si RNA on tumor growth and lung metastatic foci formation of BGC823 cells. Results The HOXC10 m RNA levels in human gastric cancer tissues were significantly higher than tumor adjacent normal tissues. The HOXC10 m RNA and protein levels in BGC823 and SGC7901 were conspicuously upregulated compared with GSE-1. The cell proliferation rate, colony formation and invasion capacities were remarkedly attenuated in HOXC10 si RNA-transfected BGC823 cells. HOXC10 si RNA-transfected BGC823 cells showed downregulation in m RNA and protein levels of vimentin and MMP-9, while E-cadherin showed upregulation. The changes of proliferation, colony formation, invasion ability and m RNA and protein levels in BGC823 transfected with HOXC10 plasmid revealed crosscurrent compared with HOXC10 si RNA transfection.HOXC10 si RNA significantly suppressed BGC823 xenografts tumor growth and inhibited the formation of lung metastatic foci. Conclusion HOXC10 may be a promising biomarker of gastric cancer diagnosis, prognosis and a potential therapeutic target.