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Wulong Xiaozheng Wan medicated serum inhibits epithelial-mesenchymal transition in human gastric carcinoma cell line BGC823 by modulation of transforming growth factor-β1/Smad signaling

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Journal of Traditional Chinese Medicine 2019年第3期39卷 380-392页

作者： Zhang Yali Wang Bingyu Guo Xueying Yang Lei Li Dandan Yuan Xingxing Department of Gastroenterology Nangang branch of Heilongjiang Academy of Traditional Chinese Medicine Harbin 150006 China Pharmacological Laboratory of Heilongjiang Academy of Traditional Chinese Medicine Harbin 150036China

OBJECTIVE:To evaluate the effect of Wulong Xiaozheng Wan medicated serum on the epithelial-mesenchymal transition (EMT) of BGC823 cell induced by transforming growth factor-β,(TGF-β,) and to explore its ***:EMT model of BGC823 was stimulated by TGF-β*** Xiaozheng Wan medicated serum and LY-364947 were used as *** proliferation and adhesion of BGC823 were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and flow cytometry was used to detect the *** invasion and migration were detected by *** level of matrix metalloproteins was detected by enzyme-linked immunosorbent *** expressions of related proteins and mRNA of EMT marker and TGF-β1/Smad signal pathway were detected by Western blot and reverse transcription-polymerase chain ***:Compared with the TGF-β1 group,Wulong Xiaozheng Wan medicated serum could inhibit the ability of proliferation,heterogeneous adhesion,invasion,and *** also promotes apoptosis and homotypic adhesion in BGC823,with a dose-dependent ***,Wulong Xiaozheng Wan medicated serum could regulate the expression of related proteins and mRNA of TGF-β1/Smad signaling pathway,and inhibit the expressions of EMT transcription factors and EMT ***:Wulong Xiaozheng Wan medicated serum inhibited epithelial-mesenchymal transition by down-regulated the expression of TβRI and the activation of TGF-β1/Smad signaling pathway.

关键词： Transforming growth factor beta1 Smad proteins Signal transduction epithelial-mesenchymal transition Matrix metalloproteinases,secreted BGC823 cell Wulong Xiaozheng Wan

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Secreted protein acidic and rich in cysteine(SPARC)induces epithelial-mesenchymal transition,enhancing migration and invasion,and is associated with high Gleason score in prostate cancer

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Asian Journal of Andrology 2019年第6期21卷 557-564页

作者： Fernanda Lopez-Moncada Maria Jose Torres Enrique A Castellon Hector R Contreras Department of Basic and Clinic Oncology Faculty of Medic泊eUniversity of ChileSantiago 8389100Chile

Secreted protein acidic and rich in cysteine(SPARC)is a matricellular protein highly expressed in bone tissue that acts as achemoattractant factor promoting the arrival of prostate cancer(PCa)cells to the bone ***,the contribution of SPARCduring the early stages of tumor progression remains *** this study,we show that SPARC is highly expressed in PCa tissueswith a higher Gleason *** stable knockdown and overexpression of SPARC in PC3 and LNCaP cells,respectively,here wedem on strate that en doge nous SPARC induces the epithelial-mesenchymal tran sition(EMT),decreasing E-cadheri n and cytokeratin18 and increasing N-cadheri n and vime ***,SPARC in duces the expression of EMT regulatory tran scription factors Snailfamily transcriptional repressor 1(Snail),Snail family transcriptional repressor 2(Slug),and zinc finger E-box binding homeobox 1(Zeb1).In addition,SPARC knockdown in PC3 cells decreases migration and invasion in vitro,without modifying cell *** results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

关键词： epithelial-mesenchymal transition invasion migration prostate cancer secreted protein acidic and rich in cysteine(SPARC)

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Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating epithelial-mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells

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Chinese Journal of Integrative Medicine 2019年第5期25卷 334-341页

作者： QIAN Ya-yun SHI You-yang LU Song-hua YANG Ting ZHAO Xue-yu YAN Yan LI Wen-yuan LIU Yan-qing Institute of Traditional Chinese Medicine and Western Medicine School of MedicineYangzhou UniversityJiangsu Province(225009)China Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases YangzhouJiangsu Province(225001)China Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Jiangsu Province(225009)China

Objective: To evaluate the effects of Celastrus Orbiculatus extracts(COE) on metastasis in hypoxiainduced hepatocellular carcinoma cells(Hep G2) and to explore the underlying molecular mechanisms. Methods:The effect of COE(160, 200 and 240 μg/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide(MTT), scratch-wound and transwell assays, respectively. Co Cl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immuno?uorescence analysis,respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner(Pepithelial-mesenchymal transition(EMT) related markers were also remarkably suppressed in a dose-dependent manner(P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1α(Hif-1α) and Twist1 were suppressed by COE. Additionally, the Hif-1α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole(YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced Hep G2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect(P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced Hep G2 cells. Conclusions: COE signi?cantly inhibited the tumor metastasis and EMT by suppressing Hif-1α/Twist1 signaling pathway in hypoxia-induced Hep G2 cell. Thus, COE might have potential effect to inhibit the progression of Hep G2 in the context of tumor hypoxia.

关键词： Celastrus Orbiculatus hepatocellular carcinoma antimetastasis epithelial-mesenchymal transition Hif-1α/Twist1 signaling pathway

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KAI1 reverses the epithelial-mesenchymal transition in human pancreatic cancer cells

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 471-477页

作者： Xu Liu Xiao-Zhong Guo Hong-Yu Li Jiang Chen Department of Gastroenterology General Hospital of Shenyang Military Area

Background: epithelial-mesenchymal transition (EMT) plays an important role in pancreatic cancer (PC). In the present study, we investigated the effects of KAI1 gene overexpression on the EMT of human PC cell lines, MIA PaCa-2 and PACN-1. Methods: Plasmids overexpressing KAI1 and pCMV were transfected into MIA PaCa-2 and PACN-1 cells, respectively. After selection of differently transfected cells by G418, KAI1 protein levels were examined by Western blotting, and transfected cells were renamed as MIA PaCa-2-K, MIA PaCa-2-p, PACN-1-K and PACN-1-p. Wound healing and Transwell migration assays were then performed comparing the two groups of cells. EMT-related markers were analyzed by Western blotting. Results: The percentage of wound closure significantly decreased in MIA PaCa-2-K cells compared with MIA PaCa-2-p and MIA PaCa-2 cells after 24, 48 and 72 h ( P < 0.05). In PACN-1-K cells, the percentage of wound closure significantly decreased as well ( P < 0.05). Numbers of invading MIA PaCa-2, MIA PaCa-2-p and MIA PaCa-2-K cells were determined as 48.0 ±15.4, 50.0 ±12.4, and 12.0 ±3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ±10.6, 31.0 ±11.4, and 8.0 ±4.2, respectively. KAI1 overexpression induced a significant upregulation of E-cadherin and also significant downregulation of Snail, vimentin, matrix metalloproteinase 2 (MMP2) and MMP9 (all P < 0.05) in PC cells. Conclusions: KAI1 reversed EMT-related marker expression and inhibited migration and invasion of PC cells. Thus, KAI1 might represent a novel potential therapeutic target for PC.

关键词： KAI1 epithelial-mesenchymal transition Pancreatic cancer

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Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer

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World Journal of Gastroenterology 2016年第30期22卷 6764-6775页

作者： Simona Gurzu Camelia Silveanu Annamaria Fetyko Vlad Butiurca Zsolt Kovacs Ioan Jung Department of Pathology University of Medicine and Pharmacy of Tirgu-Mures Department of Surgery University of Medicine and Pharmacy of Tirgu-Mures Departments of Genetics and Biochemistry University of Medicine and Pharmacy of Tirgu-Mures

epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

关键词： Angiogenesis Colorectal cancer Budding epithelial-mesenchymal transition Chemoresistance

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AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells

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Asian Pacific Journal of Tropical Medicine 2015年第12期8卷 1042-1044页

作者： Wen-Ning Li Jia-Li Wei Ming Wu Wei Wu Yun Huang Mao-Wei Xie Hui Han Department of Nephrology Hebei Medical University Department of Nephrology Hainan General Hospital Hainan Health Department

Objective:To prove whether astrocyte elevated gene-1(AEG-1) plays a role in high glucosestimulated Rho kinase activation and epithelial-mesenchymal transition(EMT) in human renal tubular epithelial(HK-2) ***:The protein levels of AEG-1,alpha-smooth muscle actin,E-cadherin and MYPT1 were determined by Western ***:AEG-1 protein level was upregulated in HK-2 cells stimulated with high ***-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced ***:Our results show that AEG-1 acts a key role in high glucoseinduced activation of Rho kinase and EMT in HK-2 cells.

关键词： Astrocyte elevated gene-1 epithelial-mesenchymal t

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Effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice

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Asian Pacific Journal of Tropical Medicine 2016年第8期9卷 774-778页

作者： Lin Song Xin Zhou Hong-Jun Jia Mei Du Jin-Ling Zhang Liang Li Oncology Department No.2 Linyi People's Hospital of Shandong Province Radiotherapy Technology Department Linyi People's Hospital of Shandong Province

Objective: To study the effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. Methods: BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. h GC-MSCs group was given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, m RNA expression of proliferation, invasion, EMT related molecules were determined. Results: 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of h GC-MSCs group were significantly higher than those of PBS group and the more the number of h GC-MSCs, the higher the tumor tissue volume; m RNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of h GC-MSCs group were higher than those of PBS group, and m RNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. Conclusions: h GC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition.

关键词： Gastric cancer mesenchymal stem cells Proliferation Invasion epithelial-mesenchymal transition

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dbEMT 2.0:An updated database for epithelial-mesenchymal transition genes with experimentally verified information and precalculated regulation information for cancer metastasis

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Journal of Genetics and Genomics 2019年第12期46卷 595-597页

作者： Min Zhao Yining Liu Chong Zheng Hong Qu School of Science and EngineeringUniversity of the Sunshine CoastMaroochydore DCQueensland4558Australia The School of Public Health Institute for Chemical CarcinogenesisGuangzhou Medical UniversityGuangzhou 510182China Center for Bioinformatics State Key Laboratory of Protein and Plant Gene ResearchCollege of Life SciencesPeking UniversityBeijing 100871China

epithelial-mesenchymal transition(EMT)is a critical cellular process in embryonic development and is also the basis for wound repair,tissue regeneration,and cancer metastasis(Zhao et al.,2015).During cancer migration and invasion,EMT involved comprehensive reprogramming processes related to cytoskeletal remodeling,cell differentiation,epigenetic regulation and metabolism(Plikus et al.,2015).In fact,the understanding of EMT in cancer development is still *** 2015.

关键词： dbEMT 2.0 epithelial-mesenchymal cancer metastasis

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Mechanisms of fibrogenesis in liver cirrhosis:The molecular aspects of epithelial-mesenchymal transition

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World Journal of Hepatology 2014年第4期6卷 207-216页

作者： Sun-Jae Lee Kyung-Hyun Kim Kwan-Kyu Park Department of Pathology Catholic University of DaeguCollege of Medicine

Liver injuries are repaired by fibrosis and *** cause of fibrosis and diminished regeneration,especially in liver cirrhosis,is still *** transition(EMT) has been found to be associated with liver *** possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types,either hepatic or bone marrow-derived cells could contribute to this *** an initial enthusiasm for the discovery of this novel pathway in fibrogenesis,more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic *** debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very *** overall result is a general confusion on the meaning and on the definition of several key *** aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions.

关键词： epithelial-mesenchymal transition Liver Fibrosis Transforming growth factor-beta1 Biological markers

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Micro-vesicles from mesenchymal stem cells over-expressing miR-34a inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition in renal tubular epithelial cells in vitro

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Chinese Medical Journal 2020年第7期133卷 800-807页

作者： Juan He Ya-Li Jiang Yan Wang Xiu-Juan Tian Shi-Ren Sun Department of Nephrology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China

Background:The use of microRNAs in the therapy of kidney disease is hampered by the difficulties in their effective ***(MVs)are known as natural carriers of small *** prior research has demonstrated that MVs isolated from mesenchymal stem cells(MSCs)are capable of attenuating kidney injuries induced by unilateral ureteral obstruction and 5/6 sub-total nephrectomy in *** present study aimed to evaluate the effects of miR-34a-5p(miR-34a)-modified MSC-MVs on transforming growth factor(TGF)-β1-induced fibrosis and apoptosis in ***:Bone marrow MSCs were modified by lentiviruses over-expressing miR-34a,from which MVs were collected for the treatment of human Kidney-2(HK-2)renal tubular cells exposed to TGF-β1(6 ng/mL).The survival of HK-2 cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)and Annexin V-Light 650/propidium iodide(PI)*** expression levels of epithelial markers(tight junction protein 1[TJP1]and E-cadherin)and mesenchymal markers(smooth muscle actin alpha(α-SMA)and fibronectin)in HK-2 cells were measured using Western blot analysis and an immunofluorescence *** addition,changes in Notch-1/Jagged-1 signaling were analyzed using Western *** were analyzed using a Student’s t test or one-way analysis of ***:MiR-34a expression increased three-fold in MVs generated by miR-34a-modified MSCs compared with that expressed in control MVs(Pepithelial-mesenchymal transition(EMT)markers were stronger than control *** effects of miR-34

关键词： Micro-vesicles mesenchymal stem cells miR-34a epithelial-mesenchymal transition

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