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基因表达谱分析揭示穿心莲抗肿瘤和抗转移作用的可能机制。

Gene expression profiling reveals the plausible mechanisms underlying the antitumor and antimetastasis effects of Andrographis paniculata in esophageal cancer.

机构信息

Department of Surgery, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), Shatin, New Territories, Hong Kong.

出版信息

Phytother Res. 2018 Jul;32(7):1388-1396. doi: 10.1002/ptr.6074. Epub 2018 Mar 26.

DOI:10.1002/ptr.6074
PMID:29577460
Abstract

Esophageal cancer (EC) is a seriously invasive malignancy with high mortality and poor prognosis. Metastasis of EC is the major cause of mortality. Our studies previously demonstrated that a herbal medicine Andrographis paniculata (AP) significantly suppressed EC growth and metastasis in vitro and in vivo. However, the underlying mechanisms responsible for these effects have not yet been systematically elucidated. In this context, gene expression profiling of AP-treated squamous EC cells (EC-109) was performed to reveal the regulatory mechanisms of AP in antitumor and antimetastasis signaling pathways using gene expression microarray analysis. Differentially expressed genes were identified by Affymetrix Gene Chip, followed by the real-time polymerase chain reaction validation. The results showed that the canonical pathways were significantly regulated by AP treatment, including multiple genes related to proliferation, apoptosis, intercellular adhesion, metastatic processes, and drug resistance, such as WNT, TGF-β, MAPK and ErbB signaling pathways, and ATP-binding cassette transporter subfamily members. This genomic study emerges candidate molecular targets and pathways to reveal the mechanisms involved in AP's effects, which provides scientific evidence to support the clinical application of AP in EC treatment.

摘要

食管癌(EC)是一种严重侵袭性的恶性肿瘤,死亡率和预后均较差。EC 的转移是导致死亡的主要原因。我们之前的研究表明,一种草药穿心莲(AP)在体外和体内显著抑制 EC 的生长和转移。然而,这些作用的潜在机制尚未得到系统阐明。在这方面,我们通过基因表达微阵列分析,对 AP 处理的鳞状 EC 细胞(EC-109)进行了基因表达谱分析,以揭示 AP 在抗肿瘤和抗转移信号通路中的调节机制。通过 Affymetrix GeneChip 鉴定差异表达基因,随后进行实时聚合酶链反应验证。结果表明,AP 处理显著调节了经典途径,包括与增殖、凋亡、细胞间黏附、转移过程和耐药性相关的多个基因,如 WNT、TGF-β、MAPK 和 ErbB 信号通路以及 ATP 结合盒转运体亚家族成员。这项基因组研究为揭示 AP 作用机制提供了候选分子靶点和途径,为 AP 在 EC 治疗中的临床应用提供了科学依据。

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