Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factor β signaling in HCT116 colon cancer cells

Autor: Jie-Ping Yu, Honggang Yu, Hao Liu, Jin-Peng Li
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Cancer Research
Epithelial-Mesenchymal Transition
Colorectal cancer
Pharmacology
Biochemistry
RNA interference
Downregulation and upregulation
Transforming Growth Factor beta
Genetics
medicine
Humans
Vimentin
doxorubicin chemoresistance
Epithelial–mesenchymal transition
RNA
Small Interfering
transforming growth factor β/Smad4 signaling
Molecular Biology
Smad4 Protein
Antibiotics
Antineoplastic
Oncogene
biology
business.industry
Cancer
Transforming growth factor beta
Articles
medicine.disease
Cadherins
HCT116 Cells
digestive system diseases
Gene Expression Regulation
Neoplastic
Oncology
colon cancer
Tumor progression
Doxorubicin
Drug Resistance
Neoplasm
Cancer research
biology.protein
Molecular Medicine
Snail Family Transcription Factors
business
Transforming growth factor
Signal Transduction
Transcription Factors
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: Doxorubicin (Dox) is a commonly used chemotherapeutic drug in human colon cancer. However, it becomes increasingly ineffective with tumor progression, the underlying mechanism of which remains to be elucidated. Emerging evidence has led to the identification of an association between chemoresistance and the acquisition of epithelial-mesenchymal transition (EMT) in cancer. However, it remains to be elucidated whether this process is involved in the development of resistance to Dox in colon cancer. In HCT116 human colon cancer cells treated with Dox (50 nmol/l), EMT was induced, and transforming growth factor (TGF)β signaling and multi-drug resistant plasma membrane glycoprotein levels were significantly increased. By contrast, silencing of Smad4, using stable RNA interference, inhibited TGFβ signaling, reversed the process of EMT and markedly increased the sensitivity of HCT116 cells to Dox. The results of the present study suggested that the combination of Dox with the downregulation of TGFβ signaling may be a potential novel therapeutic strategy with which to overcome chemoresistance during colon cancer chemotherapy.
Databáze: OpenAIRE
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