Abstract 2815: Ganoderma lucidum chemosensitizes triple negative breast cancer to carboplatin mediated by DNA damage response

Abstract

Abstract Management of triple negative breast cancer (TNBC) is challenging because of a lack of targeted therapy, its aggressive behavior and poor prognosis. Interest in using platinum agents, such as carboplatin as a line of treatment emerged from data suggesting frequent DNA repair defects in TNBC. Carboplatin resistance may occur due to multiple factors including increased activation of DNA repair mechanisms. Studies show that Ganoderma lucidum extract (GLE) sensitizes cancer cells to different anti-cancer therapies. Thus, we aim to investigate the effects of GLE in combination with carboplatin in the DDR signaling and in tumorigenesis. To study whether GLE sensitizes TNBC cells to carboplatin therapy, we treated SUM-149 and MDA-MB-231 cells with several concentrations of carboplatin, GLE, or both treatments simultaneously for 72h. Our results demonstrate that when carboplatin and GLE are used in combination the IC50s decreased in both breast cancer cell lines in comparison with treatments alone. Immunobloting assays revealed that GLE and/or the combination decrease the expression of 53BP1, p-CHK2, CHK2, p-CHK1, CHK1, p-ATR, p-ATM and p-BRCA1 in SUM-149. Accordingly, immunofluorescence studies to monitor the recruitment of DNA repair proteins 53BP1 and phosphorylated γH2AX at the lesion sites after treatments suggest that the GLE and/or carboplatin combination impair DDR. To determine tumor progression, severe combined immune deficient mice were injected with SUM-149 cells and then treated with carboplatin/GLE or carboplatin for 10 weeks. The combination significantly decrease tumor volume in comparison with the vehicle. Taken together, our results provide evidence of GLE's potential in chemosensitizing TNBC cells to carboplatin therapy affecting the DDR. These results highlight GLE's anti-breast cancer therapeutic potential. Citation Format: Ivette J. Suarez-Arroyo, Michelle M. Martinez-Montemayor. Ganoderma lucidum chemosensitizes triple negative breast cancer to carboplatin mediated by DNA damage response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2815.