Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells
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摘要Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers' great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP-treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications.
著者Yue GGL, Lee JKM, Li L, Chan KM, Wong ECW, Chan JYW, Fung KP, Lui VWY, Chiu PWY, Lau CBS
期刊名稱American Journal of Cancer Research
出版年份2015
月份1
日期1
卷號5
期次12
出版社E-CENTURY PUBLISHING CORP
頁次3570 - 3587
國際標準期刊號2156-6976
語言英式英語
關鍵詞Andrographis paniculata; anoikis; Esophageal cancer; isoandrographolide; metastasis; TM4SF3
Web of Science 學科類別Oncology

上次更新時間 2020-11-07 於 01:40