Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

摘要: Increased expression and activation of human epidermal growth factor receptor (EGFR) HER-2 have been reported in numerous cancers. The aim this study was to determine the sensitivity a large panel ovarian cancer cell lines (OCCLs) treatment with various forms small molecule tyrosine kinase inhibitors (TKIs) cytotoxic drugs. see if there any association between protein biomarkers including three putative stem (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), HER family members response these agents. 10 tumour TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well other (dasatinib, imatinib, NVP-AEW541, crizotinib) agents (paclitaxel, cisplatin doxorubicin), single or combination, determined by SRB assay. effect on cycle distribution, downstream signaling molecules migration were using flow cytometry, western blotting, IncuCyte Clear View assay respectively. Of inhibitors, irreversible pan-TKIs (canertinib, neratinib afatinib) most effective for inhibiting all cells, blocking phosphorylation EGFR, HER-2, AKT MAPK SKOV3 cells. Interestingly, while majority cells highly sensitive dasatinib, they relatively resistant imatinib (i.e., IC50 >10 µM). agents, paclitaxel OCCLs, combinations drugs, only combination NVP-AEW541 produced synergistic additive anti-proliferative examined SKOV3, Caov3, ES2). Finally, TKIs, dasatinib able reduce overexpressing We did not find significant CSC marker, members, c-MET, ALK, IGF-IR TKIs. Our results support need further investigations therapeutic potential blockers cancer, when used cancer.