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BACKGROUND The aim of this study was to investigate the synergistic effect of paclitaxel (PTX) and verapamil (VERA) on adriamycin (ADR)-resistant breast cancer (MCF-7/ADR) cells. METHODS ATP-PCA was applied to determine the inhibitory effects of PTX combined with VERA on MCF-7/ADR cells. Edu, CCK-8 and Flow cytometry (FCM), Annexin V-FITC binding and Western blot were used to analyze the effects of combination therapy with PTX and VERA on cell proliferation, progression of cell cycle and cell apoptosis. RESULTS PTX-based treatments with VERA enhanced killing effect on MCF-7/ADR cells. IC50 value of cell was significantly decreased in combination treatment compared with PTX administrated. VERA enhanced the efficacy and sensitivity of PTX to MCF-7/ADR cells. Combination of PTX and VERA could inhibit cell proliferation via arresting progression of cell cycle and promote cell apoptosis. CONCLUSION PTX, along with VERA, had a synergistic action in anti-tumor response and may be proposed as a novel treatment strategy for chemo-resistant breast cancer.