Premium
The inhibition of insulin‐like growth factor 1 receptor pathway targets putative cancer stem cells in human malignant mesothelioma
Author(s) -
Kim Yongbaek,
Kai Kiyonori,
Sills Robert C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.470.6
Subject(s) - biology , cancer stem cell , cell cycle , insulin like growth factor , cancer research , population , insulin like growth factor 1 receptor , apoptosis , cancer , stem cell , receptor , growth factor , microbiology and biotechnology , genetics , medicine , environmental health
Human malignant mesothelioma (HMM) is a fatal tumor with median survival time of 6–18 months despite of aggressive treatment schedule. Insulin‐like growth factor 1 receptor (IGF1R) pathway has known to be activated in various HMM cell lines. This study was performed to investigate the anti‐tumor effects and to elucidate an underlying mechanism of a chemical inhibitor of IGF1R pathway, AG1024, in HMM cell lines. The treatment of AG1024 decreased the cell proliferation in a dose‐dependent manner and also significantly enhanced the cytotoxicity of cisplatin which is a DNA binding anticancer drug. The inhibitory effects of AG1024 were largely dependent on the suppression of downstream pathways (PI3K and MAPK) and the changes in the expression of apoptosis‐related genes. Intriguingly, AG1024 treatment reduced the abundance of side population determined by flow cytometric analysis using Hoechst 33342 staining. The expression levels of stem‐cell related genes in the side population were altered by AG1024 treatment. The results of this study suggest that IGF1R pathway plays a crucial role in the maintenance of cancer stem cells in HMM, thus it could be a plausible target for cancer stem cell‐specific therapy to overcome chemoresistance of HMM.