Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5

Autor: Chenglin Lu, Shanhua Bao, Z. Yu, Hao Cheng, Yuehua Li, Hong Zhu, Yi-Ming Pan, M. Cao
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
medicine.medical_treatment
AMP-Activated Protein Kinases
Biochemistry
Metastasis
Cholangiocarcinoma
chemistry.chemical_compound
0302 clinical medicine
Cytotoxic T cell
General Pharmacology
Toxicology and Pharmaceutics
lcsh:QH301-705.5
Research Articles
Salinomycin
lcsh:R5-920
Antibiotics
Antineoplastic
General Neuroscience
Drug Synergism
General Medicine
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
lcsh:Medicine (General)
medicine.drug
Epithelial-Mesenchymal Transition
Cell Survival
Immunology
Biophysics
Ocean Engineering
digestive system
03 medical and health sciences
Cancer stem cell
Cell Line
Tumor
medicine
Humans
Chemotherapy
Doxorubicin
Epithelial–mesenchymal transition
Pyrans
Cell Biology
medicine.disease
digestive system diseases
030104 developmental biology
chemistry
lcsh:Biology (General)
Drug resistance
Cancer cell
Cancer research
Zdroj: Brazilian Journal of Medical and Biological Research v.50 n.10 2017
Brazilian Journal of Medical and Biological Research
Associação Brasileira de Divulgação Científica (ABDC)
instacron:ABDC
Brazilian Journal of Medical and Biological Research, Vol 50, Iss 10 (2017)
Brazilian Journal of Medical and Biological Research, Volume: 50, Issue: 10, Article number: e6147, Published: 17 AUG 2017
Popis: Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma.
Databáze: OpenAIRE
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