Combination of capecitabine and ludartin inhibits colon cancer growth in mice
Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice.
Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA. Micro-vessel density was assessed using immunohistochemical analysis.
Results: When administered separately, capecitabine and ludartin treatments significantly suppressed tumor growth in the mice model of colon cancer for 4 weeks, compared to control group. Coadministration of capecitabine and ludartin significantly inhibited tumor growth for 6 weeks (p < 0.05). Symptoms of colon cancer such as weight loss, skin discoloration and leukopenia were observed in untreated control group. However, these symptoms were completely absent in the group treated with combination of capecitabine and ludartin. The combined treatment also prevented colon cancer-induced increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from 38 to 55 days. Expression of VEGF in combination (capecitabine + ludartin) treatment group was significantly lower than in the control, i.e., untreated group (p ˂ 0.05). The combination treatment group also had significantly lower micro-vessel density in the tumor tissues, compared to the ntreated control mice (p < 0.05).
Conclusion: These results show that a combination treatment of capecitabine and ludartin effectively inhibits colon tumor growth and angiogenesis in mice via a mechanism involving suppression of VEGF expression. Thus, capecitabine and ludartin combination is a potentially uitable treatment for colon cancer.
Keywords: Colon cancer, Mice, Ludartin, Leukopenia, VEGF expression, Angiogenesis