Abstract P5-05-10: Leptin peptide receptor antagonist linked to nanoparticles: A novel adjuvant therapy for triple negative breast cancer

Abstract

Abstract Background: Obesity and high leptin levels are strongly associated with breast cancer, relapse, drug resistance, and poor patient outcomes. Over expression of leptin and its receptor, Ob-R, induce cell proliferation, angiogenesis, and metastasis in Triple Negative Breast Cancer (TNBC). This aggressive form of the disease has no targeted therapy and chemotherapeutics show several undesirable side effects. We have created a Leptin Peptide Receptor Antagonist, LPrA2, which has been shown to effectively prevent leptin signaling. LPrA2 was coupled to iron oxide nanoparticles (IONPs) and used to determine its potential use as an adjuvant to chemotherapeutics. Methods: IONPs, bound to LPrA2, were confirmed by Western Blot. TNBC cells were then treated with IONP-LPrA2 plus Cisplatin, Doxorubicin, Paclitaxel, Cyclophosphamide, and Sunitinib. Subsequently, the TNBC cells were analyzed for proliferation, cell cycle progression, and apoptosis with the Cellometer Vision Image Cytometer ®. Results: IONP-LPrA2 was found to cause a greater decrease in DNA synthesis during the S phase of the cell cycle in TNBC cells than LPrA2 alone. Additionally, IONP-LPrA2 when combined with chemotherapeutics or anti-angiogenic drugs showed synergistic effects on cell proliferation and apoptosis. Conclusion: These findings indicate that IONP-LPrA2 may be useful in the prevention and treatment of TNBC. Further IONP-LPrA2 treatment may increase the efficiency of chemotherapeutics. These results could be particularly relevant for obese patients, whom show high incidence and the poorest outcome of TNBC. Acknowledgements: This work was partially supported by the National Institutes of Health and National Cancer Institute Grant 1SC1CA138658-05 and U54 CA118638, and DOD Idea Award BC 123427 to RRGP; and facilities, and support services at Morehouse School of Medicine (NIH RR03034 and 1C06 RR18386) and NIH/NCRR grant 1G12RR026250-03. Citation Format: Tia L Harmon, Adriana Harbuzariu, Courtney D Dill, Lily Yang, Ruben R Gonzalez-Perez. Leptin peptide receptor antagonist linked to nanoparticles: A novel adjuvant therapy for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-05-10.