Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance

Autor: Hong Shen, Junli Ma, Yanlin Qu, Yan Zhang, Shan Zeng, Cao Guo, Ganlu Deng
Jazyk: angličtina
Předmět:
Male
0301 basic medicine
Cancer Research
Pathology
Organoplatinum Compounds
Leucovorin
Nestin
Mice
0302 clinical medicine
FOLFOX
Cell Movement
Antineoplastic Combined Chemotherapy Protocols
HCC
Wnt Signaling Pathway
reproductive and urinary physiology
Gene knockdown
Liver Neoplasms
EMT
Wnt signaling pathway
Hep G2 Cells
Prognosis
Up-Regulation
Gene Expression Regulation
Neoplastic
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
embryonic structures
Female
Fluorouracil
Chemoresistance
medicine.drug
medicine.medical_specialty
Carcinoma
Hepatocellular
Epithelial-Mesenchymal Transition
Mice
Nude
macromolecular substances
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Humans
Epithelial–mesenchymal transition
neoplasms
business.industry
Research
medicine.disease
digestive system diseases
030104 developmental biology
nervous system
Drug Resistance
Neoplasm
Apoptosis
Cell culture
Cancer research
business
Neoplasm Transplantation
Zdroj: Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
DOI: 10.1186/s13046-016-0387-y
Popis: Background Nestin expression has been reported to be associated with the prognosis of many solid tumors including human hepatocellular carcinoma (HCC). The present study aimed to identify the role, if any, of Nestin in the chemotherapeutic treatment of HCC. Methods We determined Nestin expression in nine HCC cell lines and 220 tissue samples of advanced HCC patients (retrospectively registered) treated with FOLFOX regimens. We examined the correlations between Nestin expression and clinicopatholgical variables and HCC prognosis. Also, we used in vitro and in vivo methods to determine the effects of Nestin expression on HCC cell invasion, migration and chemosensitivity. Results Nestin expression was significantly increased in HCC tissues and drug-resistant cell lines, and the presence of high levels of Nestin was associated with poor survival. We also showed that drug-resistance occurred in HCC cells with epithelial-mesenchymal transition (EMT), which in turn enhanced invasion ability. Nestin depletion reversed drug-resistance in the Bel-7402/5-FU and Bel-7402/ADM cell lines. Nestin knockdown enhanced chemotherapeutic efficacy in nude mice. Moreover, Nestin up-regulation in Bel-7402 was associated with the activation of Wnt/β-catenin signaling. Conclusion Our findings suggest that Nestin inhibitors may be useful for the chemotherapy of HCC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0387-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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