Small interfering RNA against PTTG: a novel therapy for ovarian cancer.
Small interfering RNA against PTTG: a novel therapy for ovarian cancer.
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DOI：
10.3892/ijo.31.1.137
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发表时间：
2007-07
影响因子：
5.2
通讯作者：
S. El-Naggar;M. Malik;S. Kakar
中科院分区：
文献类型：
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作者：
S. El-Naggar;M. Malik;S. Kakar
卵巢上皮癌是女性死亡的重要原因，占所有女性癌症相关死亡的5%。缺乏可靠的检测方法和对化疗药物的耐药性是治疗这种癌症的相当大的障碍。近年来，垂体瘤转化基因（PTTG）在包括卵巢癌在内的多种肿瘤中高水平表达。发现升高的PTTG水平诱导体外细胞转化和裸鼠肿瘤形成。因此，我们假设PTTG表达水平与肿瘤发生之间存在相关性，并且PTTG水平的下调将导致肿瘤生长的抑制。我们使用小干扰RNA（siRNA）沉默PTTG在人卵巢癌A2780细胞中的表达，并评估PTTG沉默在体外和体内肿瘤形成中的作用。针对PTTG的siRNA在mRNA和蛋白质水平上降低其表达。与载体或对照siRNA转染的细胞相比，在组成型表达PTTG siRNA的细胞中实现了50%的细胞增殖减少。此外，在PTTG siRNA稳定的细胞系中，软琼脂中的集落形成减少了70%。使用裸鼠，我们发现，动物注射组成型表达PTTG-siRNA的A2780细胞降低了肿瘤发展和肿瘤生长的发生率。总之，这些结果强烈表明，PTTG可能作为一个重要的分子靶点，发现新的抗癌药物和治疗策略。
Ovarian epithelial cancer is a significant cause of death among women, accounting for 5% of all female cancer-related fatalities. A lack of reliable detection methods and resistance to chemotherapy agents are considerable obstacles in the treatment of this cancer. Recently, high-level expression of the pituitary tumor transforming gene (PTTG) was found in a wide range of tumors, including ovarian cancers. Elevated PTTG levels were found to induce cellular transformation in vitro and tumor formation in nude mice. Therefore, we hypothesize a correlation exists between the levels of PTTG expression and tumorigenesis, and that down-regulation of PTTG levels will result in the suppression of tumor growth. We used small interfering RNA (siRNA) to silence PTTG expression in human A2780 ovarian carcinoma cells and assessed the effect of PTTG silencing in tumor formation in vitro and in vivo. The siRNA directed against PTTG reduced its expression at both the mRNA and protein levels. A fifty percent reduction in cell proliferation was achieved in cells constitutively expressing PTTG siRNA compared to vector or control-siRNA transfected cells. Furthermore, colony formation in soft agar was reduced by 70% in PTTG siRNA stable cell lines. Using nude mice, we showed that animals injected with A2780 cells constitutively expressing PTTG-siRNA decreased the incidence of tumor development and tumor growth. Taken together, these results strongly suggest that PTTG may serve as an important molecular target for the discovery of new anticancer agents and treatment strategies.