OBJECTIVE: Multidrug resistance and toxicity significantly compromise the therapeutic efficacy for sarcomas. We aimed at evaluating the effect of lutein-doxorubicin (DOX) combinatorial therapy on inhibiting S180 (Sarcoma 180) cell proliferation and tumor growth. MATERIALS AND METHODS: S180 cells in logarithmic growth phase were treated with lutein, DOX, or lutein-DOX combinatorial therapy for 48 h. The cell survival rate was determined by MTT assay. Apoptosis was detected by flow cytometry. The expression of PCNA, P53, and NF-κB was assessed by Western blot. Further, mice bearing S180 tumors received lutein, DOX, or lutein-DOX combinatorial therapy by oral gavage. RESULTS: Lutein-DOX combinatorial therapy significantly decreased the proliferation of S180 cells (p<0.01) in vitro. Also, the expression of proliferating cell nuclear antigen (PCNA) (p<0.05) and the apoptosis-relevant gene p53 were decreased, which resulted in increased cell apoptosis (p<0.05). The level of nuclear factor kappa B (NF-κB) was also decreased by the combinatorial therapy. Lutein-DOX combinatorial therapy reduced the cytotoxicity of DOX and reduced the inflammatory response. The inhibitory effect of lutein-DOX combinatorial therapy on cell proliferation was confirmed in vivo. The growth rate and size of the tumor at 30 d after treatment were significantly lower than those of the control group and DOX single therapy. CONCLUSIONS: Lutein and DOX synergistically inhibit sarcoma cell proliferation and tumor growth. This novel therapeutic regimen could potentially improve clinical outcome of sarcoma patients.