Abstract: ObjectiveTo investigate the influence of bufalin in combination with cisplatin on the proliferation of breast cancer cells and explore the possible mechanism. Methods MTT assay was used to detect the cell proliferation in blank control group（only medium），cell control group（only MCF-7 cells）and experimental groups (cells were exposed to 20 nmol／L bufalin or 20 μmol／L cisplatin alone，or their combination in a fixed ratio for 24 h). And then cell apoptosis was determined by flow cytometry after stained by propidium iodide. Expression of Met，p-Met，Src，p-Src, PARP and cleaved PARP was analyzed by Western blotting. Results MTT assay showed that cisplatin and bufalin could both suppress MCF-7 cells proliferation in a dose-dependent manner. Cisplatin and bufalin could synergistically suppress the proliferation of MCF-7 cells（0＜CI＜0.433）at concentrations of≥0.1 μmol／L and≥0.1 nmol／L，respectively. Flow cytometry analysis showed that 20 μmol／L cisplatin induced（10.7±4.8）％ apoptosis of MCF-7 cells after 24 h. Bufalin（20 nmol／L）did not induce significant apoptosis after 24 h. In contrast，the treatment of 20 nmol／L bufalin and 20 μmol／L cisplatin increased the apoptotic fraction to（40.8±8.5）％. Western Blotting analysis showed that cisplatin treatment activated Met and Src. Bufalin could significantly down-regulate the cisplatin-induced Met and Src activation and up-regulate the cleaved PARP. Conclusion Bufalin and cisplatin can synergistically suppress the proliferation and induce apoptosis of MCF-7 cells through down-regulating the cisplatin-induced activation of Met and Src.