Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer
Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer
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DOI：
10.3892/mmr.2012.1065
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发表时间：
2012-11-01
影响因子：
3.4
通讯作者：
Feng, Youji
中科院分区：
文献类型：
--
作者：
Liu, Yingtao;Tao, Xiang;Feng, Youji
卵巢癌导致的死亡比任何其他类型的女性生殖癌都要多。由于常规方法的存活率较低，因此需要开发新的治疗方法。本研究旨在探讨介体复合体19亚单位(MED19)基因沉默对卵巢癌细胞活力和肿瘤生长的影响。采用免疫组织化学方法检测MED19在人卵巢癌组织中的表达。采用慢病毒RNAi技术下调卵巢癌细胞SKOV-3和HY内源性MED19的表达。通过四甲基偶氮唑盐比色法、BrdU掺入法、克隆形成实验、细胞周期分析和裸鼠移植瘤实验，观察MED19沉默对裸鼠细胞活力和肿瘤生长的影响。资料表明，MED19在人卵巢癌组织中的表达与肿瘤的恶性程度有关。卵巢癌细胞MED19基因表达下调可显著抑制细胞增殖和集落形成，并使细胞周期停滞于G0/G1期。MED19 RNAi显著抑制裸鼠卵巢癌移植瘤生长。我们的发现表明，慢病毒介导的RNAi下调MED19基因可能在治疗人卵巢癌方面有用。
Ovarian cancer causes more deaths than any other type of female reproductive cancer. The development of new therapeutic approaches is required due to the low survival rate using routine methods. The goal of this study was to investigate the effect of the gene silencing of mediator complex subunit 19 (MED19) on cell viability and tumor growth in ovarian cancer. Immunohistochemistry was used to characterize the expression of MED19 in human ovarian cancer tissues. Lentivirus-mediated RNAi was employed to downregulate endogenous MED19 expression in SKOV-3 and HEY ovarian cancer cells. MTT assay, BrdU incorporation assay, colony formation assay, cell cycle analysis and tumor xenografts in nude mice were performed to determine the effects of MED19 silencing on cell viability and tumor growth in vitro and in vivo. The data showed that the expression of MED19 in human ovarian cancer tissues correlated with the level of tumor malignancy. The downregulation of MED19 in ovarian cancer cells significantly inhibited cell proliferation and colony formation in vitro and led to cell cycle arrest in the G0/G1 phase. MED19 RNAi significantly inhibited ovarian cancer tumor growth in engrafted nude mice. Our findings reveal that the knockdown of MED19 by lentivirus-mediated RNAi may be useful in the treatment of human ovarian cancer.