Effect of lutein and doxorubicin combinatorial therapy on S180 cell proliferation and tumor growth.

Abstract

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. 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. 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. Lutein and DOX synergistically inhibit sarcoma cell proliferation and tumor growth. This novel therapeutic regimen could potentially improve clinical outcome of sarcoma patients.