Guo Feng-Jun, Tian Jing-Yan, Jin Yue-Mei, Wang Ling, Yang Rui-Qi, Cui Man-Hua
Department of Obstetrics and Gynaecology, The Second Hospital, Jilin University, Changchun 130041, P.R. China.
Department of Urology, Second Division of the First Hospital, Jilin University, Changchun 130021, P.R. China.
Mol Med Rep. 2015 Jan;11(1):59-66. doi: 10.3892/mmr.2014.2732. Epub 2014 Oct 21.
The aim of the present study was to investigate the effects of plasmid-mediated RNA interference targeting of cyclooxygenase-2 (COX-2) on the biological behaviors of SKOV3 human ovarian cancer cells and to analyze the function of COX-2 in carcinogenesis and development of ovarian cancer. A COX-2 small hairpin (sh)RNA sequence was designed and synthesized and pGPU6-COX-2-shRNA plasmids were constructed. The recombinant vector plasmids were stably transfected into SKOV3 cells. The mRNA and protein expression of COX-2 was subsequently analyzed by quantitative polymerase chain reaction and western blot analysis, respectively. MTT and colony formation assays were used to detect the cellular proliferation ability and flow cytometry was performed to detect phase changes in the cell cycle. Finally, a Transwell assay was used to detect cell invasion. The SKOV3 cells, transfected with recombinant vector plasmids, and control cells, were injected into nude mice and the tumor emergence time, volume and weight were measured. The impact of COX-2 gene silencing on the growth of xenograft tumors in nude mice was analyzed. Following transfection of the pGPU6-COX-2-shRNA plasmid, in vitro analyses indicated that the shRNA efficiently suppressed the mRNA and protein expression of COX-2. COX-2 gene silencing significantly inhibited the proliferation and invasion ability of SKOV3 cells, leading to cell cycle arrest in G1. The tumor formation time in the interference group was significantly prolonged, and the tumor volume and weight were significantly decreased, as compared with the control group. Plasmid-mediated shRNA was shown to effectively silence COX-2 expression in SKOV3 ovarian cancer cells. It was identified that COX-2 functioned in regulating proliferation, cell cycle and invasion of ovarian cancer cells. These findings provided a theoretical basis for determining the function of COX-2 in the development of ovarian cancer and suggested that COX-2 may be an effective target for gene therapy and clinical applications.
本研究旨在探讨质粒介导的靶向环氧化酶-2(COX-2)的RNA干扰对SKOV3人卵巢癌细胞生物学行为的影响,并分析COX-2在卵巢癌发生发展中的作用。设计并合成了COX-2小发夹(sh)RNA序列,构建了pGPU6-COX-2-shRNA质粒。将重组载体质粒稳定转染至SKOV3细胞。随后分别通过定量聚合酶链反应和蛋白质印迹分析来检测COX-2的mRNA和蛋白表达。采用MTT法和集落形成试验检测细胞增殖能力,通过流式细胞术检测细胞周期的阶段变化。最后,采用Transwell试验检测细胞侵袭能力。将转染重组载体质粒的SKOV3细胞和对照细胞注射到裸鼠体内,测量肿瘤出现时间、体积和重量。分析COX-2基因沉默对裸鼠体内移植瘤生长的影响。转染pGPU6-COX-2-shRNA质粒后,体外分析表明shRNA有效抑制了COX-2的mRNA和蛋白表达。COX-2基因沉默显著抑制了SKOV3细胞的增殖和侵袭能力,导致细胞周期停滞在G1期。与对照组相比,干扰组的肿瘤形成时间显著延长,肿瘤体积和重量显著减小。结果表明,质粒介导的shRNA可有效沉默SKOV3卵巢癌细胞中COX-2的表达。研究发现COX-2在调节卵巢癌细胞的增殖、细胞周期和侵袭中发挥作用。这些发现为确定COX-2在卵巢癌发生发展中的作用提供了理论依据,并提示COX-2可能是基因治疗和临床应用的有效靶点。