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Nanoparticle-linked antagonist for leptin signaling inhibition in breast cancer

World Journal of Clinical Oncology 2017年第1期8卷 54-66页

作者： Tia Harmon Adriana Harbuzariu viola lanier Crystal C Lipsey Ward Kirlin Lily Yang Ruben R Gonzalez-Perez Department of Microbiology Biochemistry and Immunology Morehouse School of Medicine Department of Pathology and Laboratory Medicine Emory University School of Medicine

AIM To develop a leptin peptide receptor antagonist linked to nanoparticles and determine its effect on viability of breast cancer *** The leptin antagonist, LPrA2, was coupled via EDAC [1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide] to iron oxide nanoparticles(IONP-LPrA2) to increase its ***-LPrA2 conjugation was confirmed by Western blot and nanoparticle tracking *** triple negative breast cancer(TNBC) MDA-MB-231, HCC1806 and estrogen receptor positive(ER+) MCF-7 cells were analyzed for the expression of the leptin receptor, *** effects of leptin and antagonist on levels of leptin-induced STAT3 phosphorylation and cyclin D1, cell cycle progression, cell proliferation, and tumorsphere formation in breast cancer cells were *** of the chemotherapeutics [cisplatin(Cis), cyclophosphamide(CTX), doxorubicin(Dox) and paclitaxel(PTX)] to effectively reduce cell viability were *** effects of combination treatments of IONP-LPrA2 and chemotherapeutics on cell viability were *** Western blot analysis of coupling reaction products identified IONP-LPrA2 at approximately 100 ***2 significantly decreased leptin-induced p STAT3 levels in HCC1806 cells and drastically decreased cyclin D1 levels in all cell ***-LPrA2 significantly reduced leptin-induced S phase progression and cell proliferation in all breast cancer cell lines and the formation of tumorspheres in MDA-MB-231 ***, IONP-LPrA2 showed an additive effect on the reduction of breast cancer cell survival with *** plus IONP-LPrA2 produced a significant reduction in the survival of MDA-MB-231 and HCC1806 *** plus IONP-LPrA2 caused a significant decrease in the survival of MDA-MB-231 *** plus IONP-LPrA2 caused a marked reduction in the survival of HCC1806 ***, PTX plus IONP-LPrA2 did not have a major effect on the viability of the breast cancer cells when compared to PTX *** Prese

关键词： Triple negative breast cancer Obesity Leptin Leptin peptide receptor antagonist 2 Iron oxide nanoparticles Chemotherapy adjuvant

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