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小干扰 RNA 抑制激肽释放酶相关肽酶 14 基因对卵巢癌细胞的影响。

Effects of kallikrein-related peptidase 14 gene inhibition by small interfering RNA in ovarian carcinoma cells.

机构信息

Department of Obstetrics and Gynaecology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, PR China.

出版信息

Mol Med Rep. 2012 Jan;5(1):256-9. doi: 10.3892/mmr.2011.625. Epub 2011 Oct 11.

DOI:10.3892/mmr.2011.625
PMID:21993700
Abstract

Kallikrein-related peptidase 14 (KLK14) is a member of the tissue kallikrein family of proteases, which are associated with the pathogenesis of malignant tumors and are over-expressed in ovarian carcinoma. However, the mechanism through which KLK14 is implicated in ovarian cancer remains unclear. The aim of the present study was to investigate the effects of KLK14 gene inhibition by small interfering RNA (siRNA) on the growth, apoptosis and invasion of ovarian carcinoma cells in vitro. KLK14 siRNA was transiently transfected into SK-OV-3 and OVCAR-3 ovarian carcinoma cells for 48 h. The expression of KLK14 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell proliferation, apoptosis and invasion were examined by MTT, flow cytometry and Matrigel assay, respectively. The expression of survivin, caspase 9, cleaved caspase 3 and MMP2 protein was measured by Western blot analysis. The expression of KLK14 was significantly downregulated by siRNA in SK-OV-3 and OVCAR-3 cells at both the mRNA and protein levels. Following transfection with KLK14 siRNA, cell growth and invasion were significantly suppressed, and cell apoptosis was markedly induced. The expression of survivin and MMP2 was decreased, while the espression of caspase 9 and cleaved caspase 3 was increased. These results indicate that KLK14 is implicated in the malignant behavior of ovarian carcinoma cells in vitro, and that KLK14 may serve as a target for therapy of ovarian carcinoma.

摘要

激肽释放酶相关肽酶 14(KLK14)是组织激肽释放酶家族蛋白酶的成员,与恶性肿瘤的发病机制有关,在卵巢癌中过度表达。然而,KLK14 如何参与卵巢癌的发病机制尚不清楚。本研究旨在探讨小干扰 RNA(siRNA)抑制 KLK14 基因对体外卵巢癌细胞生长、凋亡和侵袭的影响。KLK14 siRNA 瞬时转染 SK-OV-3 和 OVCAR-3 卵巢癌细胞 48 h。采用逆转录-聚合酶链反应(RT-PCR)和 Western blot 分析检测 KLK14 的表达。通过 MTT、流式细胞术和 Matrigel 测定分别检测细胞增殖、凋亡和侵袭。Western blot 分析检测 survivin、caspase 9、cleaved caspase 3 和 MMP2 蛋白的表达。siRNA 可显著下调 SK-OV-3 和 OVCAR-3 细胞中 KLK14 的 mRNA 和蛋白表达。转染 KLK14 siRNA 后,细胞生长和侵袭明显受到抑制,细胞凋亡明显诱导。survivin 和 MMP2 的表达降低,而 caspase 9 和 cleaved caspase 3 的表达增加。这些结果表明,KLK14 参与了体外卵巢癌细胞的恶性行为,KLK14 可能成为治疗卵巢癌的靶点。

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J Cancer Res Clin Oncol. 2018 Jun;144(6):1109-1118. doi: 10.1007/s00432-018-2623-7. Epub 2018 Mar 15.