Synergistic Effect of SH003 and Doxorubicin in Triple-negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is highly aggressive, resulting in poor prognosis. Chemotherapy of TNBC relies on anti-cancer agents with strong cytotoxicity, but it causes several side effects with recurrence. While combinational approaches of chemotherapeutics have been highlighted as a new treatment strategy for TNBC to reduce side effects, combinations of anti-cancer agents with herbal medicines have not been reported. We recently reported that newly modified traditional Chinese medicine named SH003 inhibited TNBC growth. Considering a combinational strategy for TNBC treatment, we further studied synergistic effects of SH003 with various anti-cancer drugs in TNBC treatment. Here, we demonstrate that SH003 shows a synergistic effect with doxorubicin on TNBC treatment. Our in vitro cell viability assays revealed that SH003 and doxorubicin showed a synergistic effect in the well-defined TNBC cell line, MDA-MB-231. Moreover, we found that the combinational treatment caused Caspase-dependent apoptotic cell death. Our in vivo mouse xenograft tumor growth assays confirmed that combinational treatment of SH003 with doxorubicin repressed MDA-MB-231 tumor growth with no weight loss. Therefore, we conclude that the combinational treatment of SH003 with doxorubicin shows the synergism in TNBC treatment, and suggest that SH003 can be used together with conventional anticancer drugs in chemotherapeutic approaches. Copyright (C) 2016 John Wiley & Sons, Ltd.