中文摘要：

目的: Zoledronic 酸(ZA ) ， bisphosphonate，当前与化学疗法的代理人在联合被使用压制乳癌房间增长或胸导致癌症的 osteolysis。这研究的目的是调查在 vitro 对人的乳癌房间与自然 anticancer 混合物 plumbagin (PL ) 相结合的 ZA 的效果。

英文摘要：

Aim： Zoledronic acid （ZA）, a bisphosphonate, is currently used in combination with chemotherapeutic agents to suppress breast cancer cell proliferation or breast cancer-induced osteolysis. The aim of this study was to investigate the effects of ZA combined with a natural anticancer compound plumbagin （PL） against human breast cancer cells in vitro. Methods： Human breast cancer MDA-MB-231SArfp cells were treated with ZA, PL or a combination of ZA and PL. The cell growth, apoptosis and migration were evaluated using CCK-8 assay, flow cytometry and transwell assay, respectively. The expression of apoptosis-related proteins was measured using real-time PCR and Western blotting. Synergism was evaluated using Compusyn software, and the combination index （CI） and drug reduction index （DRI） values were determined. Results： PL or ZA alone caused mild cytotoxicity （the IC50 value at 24 h was 12.18 and above 100 pmol/L, respectively）. However, the combination of ZA and PL caused a synergistic cytotoxicity （CI=0.26）. The DRI values also showed a synergistic effect between PL and ZA, with actual values of 5.52 and 3.59, respectively. Furthermore, PL and ZA synergistically induced apoptosis and inhibited migration of the breast cancer cells. Moreover, the combination of ZA and PL decreased the expression of Notch-1, cleaved PARP, Bcl-2 and Bcl-xl, and increased the expression of cleaved caspase-3, CDKNIA and ID1. When the breast cancer cells were transfected with specific siRNA against Notch-1, the combination of ZA and PL markedly increased the expression of Bcl-2. Conclusion： Combination of ZA and PL synergistically suppresses human breast cancer MDA-MB-231SArfp cells in vitro. PL can inhibit ZA-induced activation of the Notch-1 signaling pathway and subsequently reduce the expression of Bcl-2, thus potentiating cancer cell apoptosis.