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姜黄素纳米粒子通过 NF-κB/PRL-3 信号通路对人卵巢癌细胞增殖和迁移的影响。

Effects of curcumin nanoparticles on the proliferation and migration of human ovarian cancer cells assessed through the NF-κB/PRL-3 signaling pathway.

机构信息

Department of Obstetrics and Gynecology, the Second Hospital of Jilin University, Changchun, Jilin 130021, China.

Department of Obstetrics and Gynecology, the Second Hospital of Jilin University, Changchun, Jilin 130021, China.

出版信息

Int Immunopharmacol. 2024 Nov 15;141:112964. doi: 10.1016/j.intimp.2024.112964. Epub 2024 Aug 20.

Abstract

Curcumin (CUR) exhibits potential inhibitory effects on tumor growth; however, its hydrophobicity and instability limit its clinical applications. In the present study, we developed CUR nanoparticles (CUR-NPs) and evaluated their biochemical characteristics. Cell uptake and proliferation were assessed using scratch and Transwell assays, respectively. Western blotting was performed to investigate the expression levels of proteins related to the NF-κB/PRL-3 signaling pathway, inflammatory response, cell proliferation, and cell migration in SKOV3 cells. Our findings showed that the blank vector was not cytotoxic to cells, allowing us to disregard any effects caused by the vector itself. CUR-NPs exhibited concentration- and time-dependent inhibitory effects on cell proliferation, surpassing those of CUR alone. Increasing the concentration of CUR-NPs resulted in a reduced cell scratch-healing ability and lower chamber migration capacity. Compared to the control group, expression levels of proteins associated with NF-κB/PRL-3 signaling pathway, inflammatory response (TNF-α and IL-6), cell proliferation (cyclin E1 and cyclin A1), as well as cell migration (N-cadherin and vimentin) were significantly elevated in the lipopolysaccharide (LPS) stimulation and NF-κB p65 overexpression groups. Conversely, E-cadherin expression was significantly decreased under these conditions. However, treatment with high concentrations of CUR-NPs effectively reversed these changes. These results highlight the significant ability of CUR-NPs to inhibit human ovarian cancer cell proliferation and migration, while suppressing inflammatory responses through the regulation of the NF-κB/PRL-3 signaling pathway.

摘要

姜黄素 (CUR) 表现出对肿瘤生长的潜在抑制作用;然而,其疏水性和不稳定性限制了其临床应用。在本研究中,我们开发了 CUR 纳米颗粒 (CUR-NPs) 并评估了它们的生化特性。使用划痕和 Transwell 测定分别评估细胞摄取和增殖。Western blot 用于研究 NF-κB/PRL-3 信号通路、炎症反应、细胞增殖和细胞迁移相关蛋白在 SKOV3 细胞中的表达水平。我们的研究结果表明,空白载体对细胞没有细胞毒性,因此可以忽略载体本身造成的任何影响。CUR-NPs 对细胞增殖表现出浓度和时间依赖性的抑制作用,超过了 CUR 单独的作用。增加 CUR-NPs 的浓度会降低细胞划痕愈合能力和下室迁移能力。与对照组相比,在脂多糖 (LPS) 刺激和 NF-κB p65 过表达组中,与 NF-κB/PRL-3 信号通路、炎症反应 (TNF-α 和 IL-6)、细胞增殖 (cyclin E1 和 cyclin A1) 和细胞迁移 (N-钙粘蛋白和波形蛋白) 相关的蛋白表达水平显著升高。相反,在这些条件下 E-钙粘蛋白的表达明显降低。然而,高浓度 CUR-NPs 的治疗有效逆转了这些变化。这些结果突出了 CUR-NPs 通过调节 NF-κB/PRL-3 信号通路有效抑制人卵巢癌细胞增殖和迁移以及抑制炎症反应的重要能力。

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