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Hyperthermia inhibits hypoxia-induced epithelial-mesenchymal transition in HepG2 hepatocellular carcinoma cells

World Journal of Gastroenterology 2012年第34期18卷 4781-4786页

作者： Guang-Jin Yuan Qian-Wen Li Shun-Lin Shan Wu-Ming Wang Sen Jiang Xi-Ming Xu Cancer Center the 82nd Hospital of the Chi- nese People's Liberation Army Huai'an 223001 Jiangsu Prov- ince China Cancer Center Renmin Hospital of Wuhan Uni-versity Wuhan 430060 Hubei Province China

AIM:To investigate the effect of hyperthermia on hy-poxia-induced epithelial-mesenchymal transition (EMT) in HepG2 hepatocellular carcinoma (HCC) cells, and its mechanism. METHODS:Cells were treated with hyperthermia at 43 ℃ for 0.5 h, followed by incubation under hypoxic or normoxic conditions for 72 h. Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or Western blot. The protein and mRNA expressions of Snail were also determined by Western blot and reverse transcrip-tion-polymerase chain reaction. Cell migratory capacity was evaluated. RESULTS:Hypoxia induced EMT in HepG2 cells, which was evidenced by morphological, molecular and func-tional changes, including the formation of a spindle shape and the loss of cell contact. The expression of E-cadherin was decreased but the expression of vimentin was increased; also, the migratory capability was increased by 2.2 ± 0.20-fold as compared with normoxia. However, those effects were inhibited by hyperthermia pretreatment. Furthermore, protein synthesis and mRNA expression of Snail in the cells were enhanced by hy-poxia as compared with normoxia, and also significantly inhibited by hyperthermia pretreatment. CONCLUSION:Hyperthermia may inhibit hypoxia-induced EMT in HepG2 HCC cells, and the mechanism may involve inhibition of induced expression of Snail.

关键词：过高热组织缺氧上皮间充质的转变 Hepatocellular 癌蜗牛

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Implication of the Hedgehog pathway in hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第24期23卷 4330-4340页

作者： Carminia Maria Della Corte Giuseppe Viscardi Federica Papaccio Giovanna Esposito Giulia Martini Davide Ciardiello Erika Martinelli Fortunato Ciardiello Floriana Morgillo Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale 'F. Magrassi e A. Lanzara' Università degli studi della Campania 'Luigi Vanvitelli'

The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment *** research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of *** all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC *** plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal *** re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC *** activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver *** levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical *** vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype.

关键词：刺猬上皮间充质的转变 Hepatocellular 癌 Hepatocarcinogenesis 预后

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Epithelial plasticity and cancer stem cells:Major mechanisms of cancer pathogenesis and therapy resistance

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World Journal of Stem Cells 2017年第8期9卷 118-126页

作者： Minal Garg Department of Biochemistry University of LucknowLucknow 226007India

Epithelial-mesenchymal transition(EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells(CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surfacemarkers and allow aberrant differentiation of *** facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance. Based on the current information, present review discusses and summarizes the recent advancements on the molecular mechanisms that derive epithelial plasticity and its major role in generating a subset of tumor cells with stemness properties and pathophysiological spread of tumor. This paper further highlights the critical need to examine the regulation of EMT and CSC pathways in identifying the novel probable therapeutic *** improved therapeutic strategies based on the co-administration of inhibitors of EMT, CSCs as well as differentiated tumor cells may provide improved antineoplastic response with no tumor relapse.

关键词：上皮间充质的转变 Anticancer 治疗癌症干细胞分子的致病肿瘤恶化

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Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer

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World Journal of Gastrointestinal Oncology 2017年第1期9卷 37-41页

作者： Omar Elaskalani Norbaini Binti Abdol Razak Marco Falasca Pat Metharom Platelet Research Laboratory Curtin Health Innovation and Research Institute Department of Health Sciences Curtin University School of Biomedical Sciences Curtin Health Innovation Research Institute Curtin University Metabolic Signalling Group School of Biomedical Sciences Curtin Health Innovation Research InstituteCurtin University

Pancreatic cancer has one of the worst prognoses among all cancers due to the late manifestation of identifiable symptoms and high resistance to chemo- and radiation therapies. In recent years, a cancer development phase termed epithelial-mesenchymal transition(EMT) has gained increasing research focus. The process is implicated in tumour metastasis, and emerging evidence suggests EMT also contributes or induces chemoresistance in several cancers. Nevertheless, the applicability of therapeutic targeting of EMT faces many challenges. In this mini-review, we summarise the evidence supporting the role of EMT in pancreatic cancer progression, focusing particularly on its association with chemoresistance.

关键词：上皮间充质的转变药抵抗胰腺的癌症化疗

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