MTA3通过β-hCG调控上皮性卵巢癌侵袭转移的机制研究

来源 :同济大学学报(医学版) | 被引量 : 0次 | 上传用户:yywachself
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目的探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)转移相关基因3(metastasis associated gene 3,MTA3)的表达及其与肿瘤侵袭转移的关系。方法收集晚期(FIGOⅢ-Ⅳ期)EOC术中冰冻标本(8例)及石蜡标本(21例),qRT-PCR和IHC检测卵巢部位肿瘤组织和转移瘤组织中MTA3的表达;Transwell细胞迁移实验观察下调MTA3、下调β-hCG、同时下调MTA3和β-hCG的EOC细胞株(SKOV3和ES-2)体外迁移力的变化。EOC细胞体外分别转染50、100、200 nmol/L siRNA-MTA3,qRT-PCR检测分析MTA3和β-hCG的表达相关性;qRT-PCR及Western印迹法检测分析下调MTA3对β-hCG以及上皮间质转化(EMT)标记物E-cadherin、N-cadherin表达的调控作用。结果qRT-PCR、IHC示EOC转移瘤组织中MTA3的表达显著低于卵巢部位肿瘤组织(P<0.05);Transwell细胞迁移实验示下调MTA3显著增强了EOC细胞的迁移能力(P<0.001),下调β-hCG显著降低了EOC细胞的迁移能力(P<0.001),下调MTA3下调β-hCG显著降低了EOC细胞的迁移能力(P<0.001);qRT-PCR示MTA3与β-hCG的表达呈显著负相关(P<0.05);qRT-PCR、Western印迹法示MTA3下调时,β-hCG和N-cadherin的表达显著上调,而Ecadherin的表达则显著下调。结论 MTA3可能通过β-hCG干预EM T进程,进而调控上皮性卵巢癌侵袭转移。 Objective To investigate the expression of metastasis associated gene 3 (MTA3) and its relationship with tumor invasion and metastasis in epithelial ovarian cancer (EOC). Methods Frozen specimens (8 specimens) and paraffin specimens (21 specimens) were collected from early stage (FIGO Ⅲ-Ⅳ) EOC. QRT-PCR and IHC were used to detect the expression of MTA3 in ovarian tumor tissues and metastatic tissues. Down-regulation of MTA3, down-regulation of β-hCG, down-regulation of MTA3 and β-hCG in vitro migration of SKOV3 and ES-2 cells. EOC cells were transfected with 50, 100 and 200 nmol / L siRNA-MTA3 in vitro respectively. The expression of MTA3 and β-hCG were analyzed by qRT-PCR. The expression of MTA3 and β-hCG were detected by qRT- Regulation of E-cadherin and N-cadherin expression in mesenchymal transition (EMT) markers. Results The expression of MTA3 in EOC metastases was significantly lower than that in ovarian tissues by qRT-PCR and IHC (P <0.05). Transwell cell migration assay showed that down-regulation of MTA3 significantly enhanced the migration of EOC cells (P <0.001) β-hCG significantly reduced the migration ability of EOC cells (P <0.001), down-regulation of β-hCG by MTA3 significantly reduced the migration ability of EOC cells (P <0.001); qRT-PCR showed that the expression of MTA3 and β-hCG was significantly (P <0.05). The expression of β-hCG and N-cadherin was significantly up-regulated while the expression of Ecadherin was down-regulated when qRT-PCR and Western blotting were used to down-regulate MTA3 expression. Conclusion MTA3 may interfere with the EMT process by β-hCG, and then regulate the invasion and metastasis of epithelial ovarian cancer.
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