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整合素连接激酶的沉默抑制了人卵巢癌细胞的体内致瘤性。

Silencing of integrin-linked kinase suppresses in vivo tumorigenesis of human ovarian carcinoma cells.

机构信息

Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang, PR China.

出版信息

Mol Med Rep. 2013 Mar;7(3):1050-4. doi: 10.3892/mmr.2013.1285. Epub 2013 Jan 22.

Abstract

Integrin-linked kinase (ILK) plays a role in the regulation of multiple cellular functions (e.g., promoting cell migration and proliferation, but inhibiting cell adhesion). This study investigated the inhibitory effects of ILK gene knockdown on the regulation of in vivo tumorigenesis of human ovarian carcinoma cells in nude mouse xenografts. HO-8910 cells were transfected with an ILK antisense oligonucleotide (ILK-ASO) to silence the ILK gene. Expression of ILK mRNA and protein was evaluated by RT-PCR and western blotting, respectively. The cell cycle was assessed by flow cytometric analysis. Cells with or without ILK-ASO transfection were subcutaneously injected into nude mice. The mouse body weight, tumor formation, tumor size and tumor weight were determined up to 30 days after inoculation. Tumor cells transfected with ILK-ASO had significantly decreased ILK mRNA and protein expression (P<0.01) when compared to the control cells. ILK gene silencing significantly increased the number of cells in the G0/G1 phase (67.61 vs. 43.29%, χ2=1197.15, P<0.01). After tumor cell inoculation, tumor cells transfected with ILK-ASO showed significantly delayed tumor formation when compared to control (9.10±0.74 vs. 5.30±0.67 days, respectively; P<0.01). In addition, tumor growth was suppressed in the 30 days following inoculation (P<0.01 compared with the controls). The average tumor weight in the ILK-ASO group was statistically lower than that of the control group (1.29±0.11 vs. 1.57±0.13 g, respectively; P<0.01). This study demonstrated that ILK-ASO transfection efficiently downregulated ILK expression in human ovarian carcinoma HO-8910 cells and that ILK gene silencing suppressed tumor growth in nude mice xenografts.

摘要

整合素连接激酶(ILK)在调节多种细胞功能中发挥作用(例如,促进细胞迁移和增殖,但抑制细胞黏附)。本研究探讨了 ILK 基因敲低对裸鼠异种移植中人类卵巢癌细胞体内致瘤性调节的抑制作用。HO-8910 细胞用 ILK 反义寡核苷酸(ILK-ASO)转染以沉默 ILK 基因。通过 RT-PCR 和 Western blot 分别评估 ILK mRNA 和蛋白的表达。通过流式细胞术分析评估细胞周期。将转染有或没有 ILK-ASO 的细胞皮下注射到裸鼠中。在接种后 30 天内测定小鼠体重、肿瘤形成、肿瘤大小和肿瘤重量。与对照细胞相比,转染 ILK-ASO 的肿瘤细胞的 ILK mRNA 和蛋白表达显著降低(P<0.01)。ILK 基因沉默显著增加了 G0/G1 期的细胞数量(67.61%比 43.29%,χ2=1197.15,P<0.01)。接种肿瘤细胞后,与对照相比,转染 ILK-ASO 的肿瘤细胞显示出明显延迟的肿瘤形成(分别为 9.10±0.74 天和 5.30±0.67 天;P<0.01)。此外,接种后 30 天肿瘤生长受到抑制(与对照组相比,P<0.01)。ILK-ASO 组的平均肿瘤重量明显低于对照组(分别为 1.29±0.11 克和 1.57±0.13 克;P<0.01)。本研究表明,ILK-ASO 转染可有效下调人卵巢癌 HO-8910 细胞中 ILK 的表达,ILK 基因沉默可抑制裸鼠异种移植中的肿瘤生长。

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