Potentiation of treatment efficacy against colon cancer of dopamine via elevating KLF2 expression in tumor vascular endothelial cells.

OBJECTIVE

To investigate the anti-tumor effect and potential mechanism of dopamine combined with 5-FU in colon cancer.

MATERIALS AND METHODS

Babl/c F1 generation male mice (N = 60) were inoculated with mouse C26 colon cancer cells below the pit to construct colon cancer model. Tumor-bearing mice were then divided into 4 groups (N = 8 each): model control group, dopamine group, 5-FU group and dopamine combined with 5-FU group. Dopamine (100 mg/kg/d) was intraperitoneally injected into mice. The tumor-suppressing rate was calculated. Serum VEGF concentration was gained. Tumor tissues were subjected to HE staining. KLF2 expression was determined by immunohistochemical (IHC) staining. In vitro cultured C26 cells which treated with dopamine and cell apoptosis were analyzed by flow cytometry.

RESULTS

Compared with model control group, all treatment groups showed significantly decreased tumor weight and volume (p < 0.01), increased tumor necrosis (p < 0.05), reduced serum VEGF concentration (p < 0.05), and enhanced KLF2 expression in microvessels (p < 0.05). Combined treatment in terms of dopamine combined with 5-FU had the most pronounced effect compared with both dopamine and 5-FU treatment groups individually. Dopamine single t 5-FU and 5-FU groups showed a similar proportion of viable C26 cells (p > 0.05).

CONCLUSIONS

Dopamine exerts anti-tumor effects by modulating tumor vascular homeostasis through the KLF2 signaling pathway, and potentiates the treatment efficacy of anti-tumor drug 5-FU. Our study discovered clinical significance concerning the novelty of therapeutic strategy against colon cancer.