Abstract 1215: Apigenin overcomes drug resistance by blocking signal transducer and activator of transcription 3 (STAT3) signaling in breast cancer

Abstract

Abstract Drug resistance in chemotherapy is a major obstacle for successful treatment of cancer. Drug resistance is caused by various reasons including the overexpression of P-glycoprotein (P-gp, MDR1). Development of new useful compound which overcomes drug resistance is urgent. Apigenin, a dietary flavonoid, is reported as an anti-cancer drug in vivo and in vitro. In the present study, we investigated whether apigenin is able to reverse drug resistance using adriamycin-resistant breast cancer cells (MCF-7/ADR) and xenograft mouse model. As a result, apigenin significantly decreased cell growth and colony formation in MCF-7/ADR and its parental MCF-7 cells. This growth inhibition was related with accumulation of subG0/G1 apoptotic population and increase of apoptosis cell number. Apigenin reduced the mRNA expressions of multi-drug resistance 1 (MDR1) and multi-drug resistance associated proteins (MRPs) in MCF-7/ADR cells. Apigenin also down-regulated the expression of P-gp. Apigenin reversed drug efflux from MCF-7/ADR cells resulting in Rho123 accumulation. Inhibition of drug resistance by apigenin is related with suppression of STAT3 signaling pathway. Apigenin decreased STAT-3 activation (p-STAT3) and its nuclear translocation, and inhibited the secretion of VEGF and MMP-9 which are STAT3 target genes. STAT3 inhibitor, JAK inhibitor I and HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/ADR cells. In conclusion, apigenin overcomes drug resistance, and this study advances human health. Note: This abstract was not presented at the meeting. Citation Format: Hye-Sook Seo, Jin Mo Ku, Se Hyang Hong, Hyeong Sim Choi, Jong-Kyu Woo, Bo-Hyoung Jang, Yong Cheol Shin, Seong-Gyu Ko. Apigenin overcomes drug resistance by blocking signal transducer and activator of transcription 3 (STAT3) signaling in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1215. doi:10.1158/1538-7445.AM2017-1215