PDSS2在肝细胞癌中的表达及对肝癌细胞生长和侵袭的影响

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目的探讨异戊二烯基二磷酸合酶第二亚基(PDSS2)在肝细胞癌组织及肝癌细胞株中的表达水平变化及对肝癌细胞增殖、凋亡、迁移和侵袭的影响。方法采用定量RT-PCR检测肝细胞癌组织、癌旁非癌肝组织、正常肝组织以及肝癌细胞株、正常肝细胞株PDSS2 m RNA表达水平,并分析肝细胞癌组织PDSS2 m RNA表达水平与患者临床病理特征的关系。将PDSS2表达质粒、阴性对照质粒分别转染Huh7肝癌细胞(另设空白对照,即未处理的Huh7细胞),并用MTT法检测Huh7肝癌细胞增殖能力变化,流式细胞术检测凋亡变化,Transwell法检测迁移及侵袭能力变化。结果肝细胞癌组织PDSS2 m RNA表达水平明显低于配对的癌旁非癌肝组织及正常成人肝组织,配对的癌旁非癌肝组织PDSS2 m RNA的表达水平也明显低于正常成人肝组织(P<0.05);Huh7、Hep3B和Bel-7402肝癌细胞PDSS2 m RNA表达水平均明显低于HL-7702正常肝细胞。与高表达PDSS2 m RNA者比较,低表达PDSS2m RNA的肝癌患者中其癌组织分化程度较差者(Edmondson gradeⅢ-Ⅳ)比例及存在门静脉癌栓者比例均较高;而肝细胞癌组织PDSS2 m RNA表达水平与其他临床病理参数之间,包括年龄、性别、肿瘤大小、甲胎蛋白水平均无明显相关性。与空白及阴性对照组比较,转染pc DNA3.1-PDSS2质粒的Huh7肝癌细胞增殖活性明显降低,细胞凋亡显著增加,细胞迁移和侵袭能力明显受到抑制。结论 PDSS2其表达下调参与肝细胞癌的发生发展,并且与肝细胞癌的恶性生物学特征相关;上调PDSS2表达可以抑制肝癌细胞生长和侵袭能力,PDSS2可能成为潜在的基因治疗靶点。 Objective To investigate the expression of PDSS2 in hepatocellular carcinoma and hepatocellular carcinoma cell lines and its effect on the proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells. Methods The expression of PDSS2 mRNA in hepatocellular carcinoma tissues, adjacent non-cancerous liver tissues, normal liver tissues, hepatocellular carcinoma cell lines and normal hepatocellular carcinoma cells was detected by quantitative RT-PCR. The expression of PDSS2 mRNA in hepatocellular carcinoma tissues was analyzed. Clinicopathological characteristics of the relationship. The PDSS2 expression plasmid and the negative control plasmid were respectively transfected into Huh7 hepatoma cells (untreated Huh7 cells were also set as blank control). The proliferation of Huh7 hepatoma cells was detected by MTT assay. The changes of apoptosis were detected by flow cytometry. Detection of migration and invasion ability changes. Results The expression level of PDSS2 mRNA in hepatocellular carcinoma tissues was significantly lower than that in paired paracancer non-cancerous liver tissues and normal adult liver tissues. The expression of PDSS2 mRNA in paired paracancer tissues was also significantly lower than that in normal adult liver tissues P <0.05). The expression levels of PDSS2 mRNA in Huh7, Hep3B and Bel-7402 hepatoma cells were significantly lower than those in HL-7702 normal hepatocytes. Compared with those with high expression of PDSS2 mRNA, the percentage of Edmondson gradeⅢ-Ⅳ and the presence of portal vein thrombosis were significantly higher in HCC patients with low expression of PDSS2mRNA. However, PDSS2m RNA expression levels and other clinical and pathological parameters, including age, gender, tumor size, alpha-fetoprotein levels were not significantly correlated. Compared with blank control group and blank control group, the proliferation activity of Huh7 hepatoma cells transfected with pcDNA3.1-PDSS2 plasmid was significantly decreased, apoptosis was significantly increased, and cell migration and invasion ability was significantly inhibited. Conclusion The down-regulation of PDSS2 expression is involved in the development of hepatocellular carcinoma and is related to the malignant biological characteristics of hepatocellular carcinoma. Upregulation of PDSS2 can inhibit the growth and invasion of hepatocellular carcinoma cells. PDSS2 may be a potential gene therapy target.
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