Salidroside improves the hypoxic tumor microenvironment and reverses the drug resistance of platinum drugs via HIF-1α signaling pathway

Autor: Weilong Zhong, Qiang Zhang, Kailiang Qiao, Lan Yang, Guang Yang, Jia-Huan Yang, Yanrong Liu, Yuan Qin, Huijuan Liu, Cheng Yang, Tao Sun, Denghui Zhai, Meng Li, Yuanhao Tang
Rok vydání: 2018
Předmět:
Hypoxic tumor microenvironment
0301 basic medicine
Research paper
OXA
oxaliplatin

Drug resistance
Mice
chemistry.chemical_compound
0302 clinical medicine
Glucosides
Cell Movement
Tumor Microenvironment
Hypoxia
media_common
DDP
cisplatin

Chemistry
Liver Neoplasms
Salidroside
General Medicine
ECM
extracellular matrix

030220 oncology & carcinogenesis
HCC
hepatocellular carcinomas

medicine.symptom
EMT
epithelial–mesenchymal transition

Signal Transduction
medicine.drug
Drug
Epithelial-Mesenchymal Transition
Cell Survival
media_common.quotation_subject
PCNA
proliferating cell nuclear antigen

Sal
salidroside

HIF-1α
Antineoplastic Agents
General Biochemistry
Genetics and Molecular Biology

03 medical and health sciences
Phenols
In vivo
Cell Line
Tumor

parasitic diseases
medicine
Animals
Humans
Epithelial–mesenchymal transition
Cisplatin
Gene Expression Profiling
MDR
multi-drug resistance

MRP
multidrug resistance-associated protein

Computational Biology
CI
combination index

Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit

Xenograft Model Antitumor Assays
Oxaliplatin
Disease Models
Animal

030104 developmental biology
Drug Resistance
Neoplasm

HIF-1α
hypoxia-inducible factor 1α

Cancer research
Zdroj: EBioMedicine
ISSN: 2352-3964
Popis: Background Hypoxia commonly occurs in solid tumors. The hypoxia in the center of solid tumors considerably decreases the chemosensitivity of tumor cells and induces epithelial–mesenchymal transition (EMT) as well as drug resistance of antitumor drugs. Methods Here, the effects of salidroside (Sal) combined with platinum drugs on human hepatocellular carcinoma were examined in vitro and in vivo. We investigated the antitumor effects of Sal by inhibiting the drug resistance and explained its mechanism in inhibiting tumor growth. Findings The results showed that Sal co-administration reverses the drug resistance of platinum drugs and suppressed metastasis induced by the hypoxic tumor microenvironment. Sal promoted the degradation of HIF-1α. In conclusion, Sal significantly increased the sensitivity to platinum drugs and inhibited hypoxia-induced EMT in hepatocellular carcinoma (HCC) through inhibiting HIF-1α signaling pathway. Interpretation Therefore, Sal may be an effective platinum drug sensitizer that can improve the chemotherapeutic efficacy in patients with HCC.
Databáze: OpenAIRE