中药左金丸提取物在减弱结肠癌细胞中Wnt/β-连环蛋白信号传导方面模拟了5-羟色胺受体1D拮抗剂的作用。
Extracts of Zuo Jin Wan, a traditional Chinese medicine, phenocopies 5-HTR1D antagonist in attenuating Wnt/β-catenin signaling in colorectal cancer cells.
作者信息
Pan Jielu, Xu Yangxian, Song Haiyan, Zhou Xiqiu, Yao Zemin, Ji Guang
机构信息
Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Department of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
出版信息
BMC Complement Altern Med. 2017 Nov 28;17(1):506. doi: 10.1186/s12906-017-2006-7.
BACKGROUND
In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW remains unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues. The present study aimed at investigating effect of ZJW extracts on the biological function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/β-catenin signaling pathway.
METHODS
In this study, the effect of ZJW extracts on 5-HTR1D expression and Wnt/β-catenin signaling pathway were investigated and contrasted with GR127935 (GR), a known 5-HTR1D antagonist, using the CRC cell line SW403. The cells were respectively treated with GR127935 and different doses of ZJW extracts. Proliferation, apoptosis, migration, and invasion of SW403 cells were compared between ZJW and GR127935 treatments. The expression of 5-HTR1D and signaling molecules involved in the canonic Wnt/β-catenin pathway were determined by Western blot analysis.
RESULTS
After ZJW extracts treatment and GR127935 treatment, G1 arrest in cell cycle of SW403 was increased. Cell apoptosis was pronounced, and cell migration and invasion were suppressed. SW403 cells showed a dose-dependently decreased expression of 5-HTR1D, meanwhile, β-catenin level was significantly decreased in nucleus of cells cultured with GR127935. Treatment of ZJW extracts dose-dependently resulted in decreased 5-HTR1D and a concomitant reduction in the Wnt/β-catenin signal transduction, an effect indistinguishable from GR127935 treatment.
CONCLUSION
The anticancer activity of ZJW extracts may be partially achieved through attenuation of the 5-HTR1D-Wnt/β-catenin signaling pathway.
背景
体外和体内研究表明，中药方剂左金丸（ZJW）具有抗癌特性。然而，ZJW作用的潜在机制仍不清楚。已表明5-羟色胺受体（5-HTR）的各种亚型在致癌作用和癌症转移中发挥作用。其中，5-HTR1D在结肠直肠癌（CRC）细胞系和组织中高表达。本研究旨在探讨ZJW提取物对CRC细胞生物学功能、5-HTR1D表达以及Wnt/β-连环蛋白信号通路分子的影响。
方法
在本研究中，使用CRC细胞系SW403，研究ZJW提取物对5-HTR1D表达和Wnt/β-连环蛋白信号通路的影响，并与已知的5-HTR1D拮抗剂GR127935（GR）进行对比。细胞分别用GR127935和不同剂量的ZJW提取物处理。比较ZJW和GR127935处理之间SW403细胞的增殖、凋亡、迁移和侵袭。通过蛋白质印迹分析确定5-HTR1D的表达以及经典Wnt/β-连环蛋白途径中涉及的信号分子。
结果
ZJW提取物处理和GR127935处理后，SW403细胞周期中的G1期阻滞增加。细胞凋亡明显，细胞迁移和侵袭受到抑制。SW403细胞显示5-HTR1D表达呈剂量依赖性降低，同时，在用GR127935培养的细胞细胞核中，β-连环蛋白水平显著降低。ZJW提取物处理剂量依赖性地导致5-HTR1D降低，并伴随Wnt/β-连环蛋白信号转导减少，这一效应与GR127935处理无差异。
结论
ZJW提取物的抗癌活性可能部分通过减弱5-HTR1D-Wnt/β-连环蛋白信号通路来实现。
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