nm23-H1基因表达与卵巢癌转移的相关性

背景与目的：转移是卵巢癌治疗失败及患者死亡的首要原因。然而,目前对卵巢癌转移潜能的分子机制知之不多。本研究旨在筛选高频转移卵巢恶性肿瘤细胞,分析卵巢癌高频转移细胞模型中nm23．H1基因表达与肿瘤转移特性的相关性,为系统实验研究和临床实践提供依据。方法：通过反复动物接种和体外培养,观察动物肺转移状况,筛选高频转移细胞株,比较原发肿瘤和转移肿瘤的特征,并应用Northem blot和Westem blot方法测定各类肿瘤细胞nm23 mRNA和蛋白表达水平。结果：8株卵巢恶性肿瘤细胞中,4株有较高转移潜能,多次培养接种可筛选出高频转移细胞亚群。各类细胞nm23mRNA和蛋白表达水平与肿瘤转移特性呈负相关(r=0．96,P=0．0001)。结论：由基因分子水平决定的肿瘤转移趋势在不同肿瘤种类及细胞亚群中有明显差异;卵巢癌中nm23 mRNA和蛋白的表达与其转移能力的降低有密切关系,可作为判定卵巢癌预后的敏感指标。

Association between Nm23-H1 gene expression and metastasis of ovarian carcinoma

BACKGROUND & OBJECTIVE: Metastasis is the leading cause of treatment failure and death of ovarian cancer. However, The molecular mechanisms associated with acquisition of metastatic ability in ovarian cancer are poorly understood. This study aimed at selecting the ovarian carcinoma cell lines with high frequency metastasis and studing the association between nm23-H1 gene expression in the model of ovarian carcinoma cells so as to provide the evidence for systematical experimental studying and clinical practice. METHODS: Each ovarian cancer cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting the number of lung tumor foci at different time. The metastatic tumors were cultured in vitro, then established substrain and transplanted subcutaneously three times. The mRNA and protein level of nm23 in 8 human ovarian cancer cell lines were examined. RESULTS: Four cell lines have high frequency metastatic potentiality. The subpopulation of cells with high frequency metastasis could be screened by injection several times. The expression of nm23 mRNA and protein in human ovarian cancer cells is inversely related to metastatic behavior in experimental animals ( r =0.96, P=0.0001 ). CONCLUSION: The difference of metastatic potential, which was determined by genetic and molecular levels, was significant among different type of cell lines and subtypes. The expression of nm23 mRNA and protein in human ovarian carcinomas were correlated closely with the reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator of ovarian cancer.