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      Anti-metastatic effects of Aidi on human esophageal squamous cell carcinoma by inhibiting epithelial-mesenchymal transition and angiogenesis

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          Abstract

          Aidi injection, a proprietary Chinese medicine, has been widely used for the treatment of cancer. However, its effects and potential mechanism in esophageal squamous cell carcinoma (ESCC) have not yet been characterized. The aim of the present study was to identify the mechanism underlying the anti-metastatic effects of treatment with Aidi. To test the effects and mechanism, EC9706 and KYSE70 cells were selected for in vitro experiments. In vivo, the anti-metastatic effects of Aidi injection on a nude mouse peritoneal metastasis model were examined, and the mechanisms were assessed with immunohistochemical staining. A cell proliferation assay demonstrated that treatment with more than 3 mg/ml Aidi for 24 or 48 h significantly inhibited the proliferation of EC9706 (P<0.01) and KYSE70 cells (P<0.05, P<0.01). Subsequent experiments assessed cell migration, invasion and vasculogenic mimicry (VM) formation, with 5-fluorouracil serving as a positive control. It was observed that treatment with Aidi inhibited cell migration, invasion and VM formation. Furthermore, it was identified that treatment with Aidi inhibited epithelial-mesenchymal transition (EMT) signaling and the expression of vascular endothelial growth factor A (VEGF-A) in EC9706 and KYSE70 cells, using western blotting. In the in vivo experiments, Aidi injection effectively suppressed tumor metastasis in the mouse tumor model. Additionally, the expression of vimentin and vascular endothelial growth factor was decreased, and the expression of cadherin-1 was increased in the tumor tissue. The present results suggested that treatment with Aidi may inhibit tumor metastasis in ESCC through the inhibition of EMT signaling and angiogenesis.

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          Most cited references30

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          Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry.

          The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay. The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern in vivo and in a three-dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.
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            Targeting EMT in cancer: opportunities for pharmacological intervention.

            The spread of cancer cells to distant organs represents a major clinical challenge in the treatment of cancer. Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of metastasis in some cancers by conferring an invasive phenotype. As well as facilitating metastasis, EMT is thought to generate cancer stem cells and contribute to therapy resistance. Therefore, the EMT pathway is of great therapeutic interest in the treatment of cancer and could be targeted either to prevent tumor dissemination in patients at high risk of developing metastatic lesions or to eradicate existing metastatic cancer cells in patients with more advanced disease. In this review, we discuss approaches for the design of EMT-based therapies in cancer, summarize evidence for some of the proposed EMT targets, and review the potential advantages and pitfalls of each approach.
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              Esophageal cancer statistics in China, 2011: Estimates based on 177 cancer registries

              Abstract Background Esophageal cancer has been a common cancer in China for many years. Using the most recent data collected from the National Central Cancer Registry, we present estimates of the esophageal cancer burden in China in 2011. Methods Age‐specific incidence and mortality rates by gender and area for 18 age groups were calculated based on data from 177 qualified population‐based cancer registries. The number of new cases of esophageal cancer and cancer deaths were computed by multiplying these rates by the 2011 population. Crude incidence and mortality rates of esophageal cancer were estimated. Results The estimated number of new esophageal cancer cases and deaths were 291 238 and 218 957, respectively. The crude incidence and mortality rates for esophageal cancer were 21.62/100 000 and 16.25/100 000, respectively. The age‐standardized incidence and mortality rates by world population were 15.83/100 000 and 11.62/100 000, respectively. Both the incidence and mortality rates of esophageal cancer were higher in rural areas than in urban areas, and in men than in women. The age‐specific esophageal cancer incidence and mortality rates increased with age. In China, squamous cell cancer was the most common pathological type of the disease. Conclusion Esophageal cancer remains a major public health issue in China. Primary and secondary prevention are essential for disease control.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                July 2018
                04 May 2018
                04 May 2018
                : 18
                : 1
                : 131-138
                Affiliations
                [1 ]Department of Thoracic Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
                [2 ]Institute of Combining Traditional Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
                [3 ]Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
                Author notes
                Correspondence to: Dr Zhiyan Ding, Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 368 Hanjiang Middle Road, Yangzhou, Jiangsu 225009, P.R. China, E-mail: dingzy39@ 123456163.com
                [*]

                Contributed equally

                Article
                mmr-18-01-0131
                10.3892/mmr.2018.8976
                6059661
                ef71ee98-8ce2-49fa-bc43-125a6856e1a6
                Copyright: © Shi et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 29 November 2017
                : 05 April 2018
                Categories
                Articles

                aidi injection,metastasis,angiogenesis,emt,escc
                aidi injection, metastasis, angiogenesis, emt, escc

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