Bag-1 silencing enhanced chemotherapeutic drug-induced apoptosis in MCF-7 breast cancer cells affecting PI3K/Akt/mTOR and MAPK signaling pathways.
作者： Pelin Ozfiliz Kilbas , Izzet Mehmet Akcay , Gizem Dinler Doganay , Elif Damla Arisan
DOI: 10.1007/S11033-018-4540-X
关键词:
摘要: The multifunctional anti-apoptotic Bag-1 protein has important roles in apoptosis, proteasome-mediated degradation, transcriptional regulation, and intracellular signaling. promotes cell survival proliferation, is overexpressed breast cancer. Therefore, Bag-1-targeted therapy might be a promising strategy to treat However, the effects of silencing combination with conventional chemotherapeutic drugs on viability major signaling pathways have not yet been fully investigated cancer cells. In this study, we cytotoxic silencing, alone cisplatin or paclitaxel treatment, MCF-7 knockdown by shRNA siRNA transfection sensitized cells apoptosis induced paclitaxel. Combination drug treatment more potently downregulated pro-survival PI3K/Akt/mTOR p44/42 mitogen activated kinase (MAPK) pathways, upregulated stress-activated p38 SAPK/JNK MAPK pathways. Bag-1-silenced drug-treated had also highly reduced proliferative capacity, cyclin–cyclin dependent complexes tumor suppressors p21 Rb. These results overall indicated that enhanced cisplatin- paclitaxel-induced cytotoxicity through multiple conclusion, targeted enhance therapeutic potential anti-cancer
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