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Nicotinic receptors modulate antitumor therapy response in triple negative breast cancer cells

World Journal of Clinical Oncology 2022年第6期13卷 505-519页

作者： Alejandro Español Yamila Sanchez Agustina Salem jaqueline obregon Maria Elena Sales Laboratory of Immunopharmacology and Tumor Biology CEFYBO CONICET University of Buenos AiresBuenos Aires C1121ABGArgentina

BACKGROUND Triple negative breast cancer is more aggressive than other breast cancer subtypes and constitutes a public health problem worldwide since it has high morbidity and mortality due to the lack of defined therapeutic *** to chemotherapy complicates the course of patients’*** authors have highlighted the participation of nicotinic acetylcholine receptors(nAChR)in the modulation of conventional chemotherapy treatment in cancers of the ***,in breast cancer,less is known about the effect of nAChR activation by nicotine on chemotherapy treatment in smoking *** To investigate the effect of nicotine on paclitaxel treatment and the signaling pathways involved in human breast MDA-MB-231 tumor *** Cells were treated with paclitaxel alone or in combination with nicotine,administered for one or three 48-h *** effect of the addition of nicotine(at a concentration similar to that found in passive smokers’blood)on the treatment with paclitaxel(at a therapeutic concentration)was determined using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide *** signaling mediators involved in this effect were determined using selective *** also investigated nAChR expression,and ATP“binding cassette”G2 drug transporter(ABCG2)expression and its modulation by the different treatments with Western *** effect of the treatments on apoptosis induction was determined by flow cytometry using annexin-V and 7AAD *** Our results confirmed that treatment with paclitaxel reduced MDA-MB-231 cell viability in a concentration-dependent manner and that the presence of nicotine reversed the cytotoxic effect induced by paclitaxel by involving the expression of functionalα7 andα9 nAChRs in these *** action of nicotine on paclitaxel treatment was linked to modulation of the protein kinase C,mitogen-activated protein kinase,extracellular signal-regulated kinase,and NF-κB signaling pathways,

关键词： Breast cancer Paclitaxel Nicotinic acetylcholine receptors Drug therapy Signal transduction Drug transporter

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