Rao Yu-Mei, Ji Mei, Chen Cai-Hong, Shi Hui-Rong
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Center of Reproductive Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
J Huazhong Univ Sci Technolog Med Sci. 2013 Apr;33(2):266-271. doi: 10.1007/s11596-013-1109-8. Epub 2013 Apr 17.
Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.
卵巢癌是致死率排名第五的妇科恶性肿瘤。转移相关基因1(MTA1)在许多具有高转移潜能的恶性肿瘤中过表达。本研究调查了通过RNA干扰下调A2780卵巢癌细胞中MTA1的表达是否会影响细胞的增殖、失巢凋亡、迁移、侵袭和黏附,并研究MTA1基因治疗卵巢癌的潜力。用有效的Mta1基因小干扰RNA转染后,通过MTT法、流式细胞术、伤口愈合试验、Transwell试验和黏附试验检测对A2780细胞增殖、失巢凋亡、迁移、侵袭和黏附的影响。评估对照细胞和转染细胞中PTEN、β1整合素、MMP-9、磷酸化AKT(Ser473)的表达水平以及总AKT活性。结果表明,Mta1-siRNA转染介导的MTA1抑制降低了细胞侵袭、迁移和黏附,并诱导细胞失巢凋亡增加,但A2780癌细胞的增殖未发现显著差异。此外,β1整合素、MMP-9和磷酸化AKT蛋白水平显著下调,而PTEN显著上调。这些结果表明,MTA1在卵巢癌细胞转移中起重要作用。MTA1可作为卵巢癌另一个新的潜在治疗靶点。