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人参皂苷 Rg3 通过 TGF-β/Smad 和 ERK 信号通路抑制体外瘢痕成纤维细胞增殖、血管生成和胶原合成。

Ginsenoside Rg3 inhibits keloid fibroblast proliferation, angiogenesis and collagen synthesis in vitro via the TGF‑β/Smad and ERK signaling pathways.

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

出版信息

Int J Mol Med. 2018 Mar;41(3):1487-1499. doi: 10.3892/ijmm.2018.3362. Epub 2018 Jan 4.

DOI:10.3892/ijmm.2018.3362
PMID:29328420
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5819908/
Abstract

A wide range of therapeutic options exists for the treatment of keloids, all of which have their own strengths; however, a high risk of side‑effects and frequent recurrence remains. Therefore, the present study aimed to identify improved therapeutic approaches or drugs for the treatment of keloids. Ginsenoside Rg3 (Rg3) has been reported to exert numerous antitumor effects, thus indicating that Rg3 may be a potential therapeutic agent that targets keloids. The present study determined the effects of Rg3 on human keloid fibroblasts (KFs) in vitro, and further explored the associated molecular and cellular mechanisms. Keloid scar specimens were obtained from patients, aged between 22 and 35 years, without systemic diseases and primary cells were isolated from keloid tissues. In each assay, KFs were divided into three groups and were cultured in medium with or without various concentrations of Rg3 (50 or 100 µg/ml). Cell viability assay, flow cytometry, quantitative polymerase chain reaction, cell migration assay, immunofluorescence staining, western blot analysis, Transwell cell invasion assay and immunohistochemical analysis were used to analyze the KFs and keloid explant cultures. The results of the present study demonstrated that Rg3 was able to exert an inhibitory effect on the transforming growth factor‑β/Smad and extracellular signal‑regulated kinase signaling pathways in KFs. The proliferation, migration, invasion, angiogenesis and collagen synthesis of KFs were markedly suppressed following treatment with Rg3. Furthermore, the results of an ex vivo assay indicated that Rg3 inhibited angiogenesis and reduced collagen accumulation in keloids. Significant statistical differences existed between the control and Rg3‑treated groups (P<0.05). All of these experimental results suggested that Rg3 may serve as a reliable drug for the treatment of patients with keloids.

摘要

存在多种治疗瘢痕疙瘩的方法,每种方法都有其自身的优势,但存在副作用风险高和频繁复发的问题。因此,本研究旨在寻找治疗瘢痕疙瘩的改良治疗方法或药物。已报道人参皂苷 Rg3(Rg3)具有多种抗肿瘤作用,这表明 Rg3 可能是一种针对瘢痕疙瘩的潜在治疗药物。本研究旨在体外观察 Rg3 对人瘢痕疙瘩成纤维细胞(KF)的影响,并进一步探讨其相关的分子和细胞机制。从年龄 22-35 岁、无系统性疾病的患者中获取瘢痕疙瘩标本,从瘢痕疙瘩组织中分离出原代细胞。在每个实验中,将 KF 分为三组,分别在含有不同浓度 Rg3(50 或 100μg/ml)的培养基中进行培养。通过细胞活力测定、流式细胞术、实时定量聚合酶链反应、细胞迁移实验、免疫荧光染色、Western blot 分析、Transwell 细胞侵袭实验和免疫组织化学分析来分析 KF 和瘢痕疙瘩组织培养物。本研究结果表明,Rg3 能够抑制 KF 中的转化生长因子-β/Smad 和细胞外信号调节激酶信号通路。Rg3 处理后,KF 的增殖、迁移、侵袭、血管生成和胶原合成明显受到抑制。此外,离体实验结果表明 Rg3 抑制了血管生成并减少了瘢痕疙瘩中的胶原积累。对照组和 Rg3 处理组之间存在显著的统计学差异(P<0.05)。所有这些实验结果表明,Rg3 可能是治疗瘢痕疙瘩患者的可靠药物。

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