Targeting epidermal growth factor receptor pathway with irreversible tyrosine kinase inhibitor
| Autor: | Asuman Demiroglu-Zergeroglu, Fatma Sagir |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway medicine.drug_class Chemistry Biochemistry (medical) Clinical Biochemistry Epidermal Growth Factor Receptor Pathway Biochemistry Tyrosine-kinase inhibitor 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis medicine Cancer research Molecular Biology Protein kinase B |
| Zdroj: | Turkish Journal of Biochemistry. 44:62-69 |
| ISSN: | 1303-829X |
| Popis: | BackgroundMalignant mesothelioma (MM) is an endemic disease around central Anatolia region in Turkey, where people are exposed to erionite- and asbestos-contaminated soil. Aberrant EGFR signalling has implicated in several cancers including MMs. Tyrosine kinase inhibitors are new treatment options harbouring deregulated signalling network components. In this study, we aimed to investigate anti-proliferative effect of CL-387,785 in MM cells.Materials and methodsAlteration of cell proliferation was evaluated with using MTS assay. Profile of EGFR, ERK, AKT, JNK and p38 proteins and ELK-1, JUN, STAT1, STAT3 and STAT5 genes were analysed by western blot and RT-PCR, respectively.ResultsViability of MM cells was inhibited in dose- and time-dependent manner. CL-387,785 affected MM cells earlier and at higher extent compared to the mesothelial cells. CL-387,785 treatments suppressed EGF-induced phosphorylation of EGFR, ERK, AKT, STAT3 and STAT5 but not SAPK/JNK and p38 in SPC212 cells. RT-PCR analysis showed that expression of p21 increased, while Cyclin D and c-jun expressions decreased in SPC212 cells. However, ELK-1, STAT3 and STAT5, expressions did not change.ConclusionOur results propose that CL-387,785 could be an efficacious agent in the treatment of MMs with uncontrolled EGFR signalling. |
| Databáze: | OpenAIRE |
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