Krüppel‐like factor 4 promotes high‐mobility group box 1‐induced chemotherapy resistance in osteosarcoma cells

Autor: Qingping Jin, Muliang Ding, Jiangdong Ni, Junjie Wang, Deye Song, Ke Liu, Jun Huang
Rok vydání: 2016
Předmět:
0301 basic medicine
Krüppel‐like factor 4
Cancer Research
Transcription
Genetic
Carcinogenesis
medicine.medical_treatment
Kruppel-Like Transcription Factors
Antineoplastic Agents
Bone Neoplasms
Drug resistance
high‐mobility group box 1
Biology
Kruppel-Like Factor 4
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Cell Line
Tumor
medicine
Humans
Chemotherapy
Doxorubicin
HMGB1 Protein
Promoter Regions
Genetic
Clonogenic assay
Cisplatin
Osteosarcoma
Binding Sites
drug resistance
Original Articles
General Medicine
medicine.disease
Gene Expression Regulation
Neoplastic
Methotrexate
030104 developmental biology
Oncology
Drug Resistance
Neoplasm
KLF4
030220 oncology & carcinogenesis
embryonic structures
Immunology
Cancer research
Original Article
Protein Binding
medicine.drug
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.12864
Popis: Osteosarcoma is the most common primary malignant bone tumor, and the frequent acquisition of chemoresistance is often an obstacle to achieving favorable outcomes during chemotherapy. Recently, Krüppel‐like factor 4 (KLF4) has been shown to be associated with chemotherapy resistance in a few tumors; however, the involvement of KLF4 in chemotherapy resistance in osteosarcoma cells remains unknown. In this study, quantitative real‐time PCR and western blot analysis revealed that KLF4 expression was significantly increased in response to cisplatin, methotrexate and doxorubicin treatment in osteosarcoma cells, and knockdown of KLF4 increased sensitivity to these anticancer drugs by decreasing cellular clonogenic ability and increasing apoptosis. Moreover, our data suggest that KLF4‐regulated drug resistance might, at least partially, positively regulate high‐mobility group box 1 (HMGB1), which was found to be a significant contributor to chemoresistance in osteosarcoma cells in our previous study. In summary, this study highlights the significance of KLF4/HMGB1 interaction in regulating chemotherapy resistance, and suggests that targeting KLF4/high‐mobility group box 1 may be a therapeutic strategy for osteosarcoma chemotherapy.
Databáze: OpenAIRE
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