Abstract
Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and RKO cells were examined and the results showed that migration and invasion capacities of HCT116 cells and RKO cells were reduced by administering 5-Fu/P85 copolymer micelles in vitro and in vivo which indicating an effectively activity. Interestingly, the content of CD133 + CXCR4+ cells in HCT116 cancer cells and RKO cells treated by 5-Fu/P85 copolymer micelles was decreased. Importantly, the epithelial-mesenchymal transition (EMT) of CD133 + CXCR4+ cells, which was strongly associated with liver metastasis of colon cancer, was also suppressed by giving 5-Fu/P85 copolymer micelles. The results indicated that 5-Fu/P85 copolymer micelles could inhibit the growth and metastasis of colon cancer, which could be attributed to the decrease of the content of CD133 + CXCR4+ cells and suppression of EMT of CD133 + CXCR4+ cells.
Highlights
Colon cancer is widely spread cancer around the world and currently ranked as the fourth common cause of cancer deaths[1]
The 5-Fu from nano-micelles was investigated by high-performance liquid chromatography (HPLC)
We detected the content of CD133 + CXCR4+ cells in HCT116 cells with different indicated treatments by flow cytometry and the results showed that the content of CD133 + CXCR4+ cells in HCT116 cells pretreated with 5-Fu/P85 copolymer micelles was less than that of HCT116 cells pretreated with 5-Fu or P85 alone group (Fig. 5A,C)
Summary
Colon cancer is widely spread cancer around the world and currently ranked as the fourth common cause of cancer deaths[1]. There is no effective treatment for liver metastasis of colon cancer. The chemosensitisation effect of pluronic has been recognized as an effective means of causing an elevation of cancer cell apoptosis by modulating the fluidity of the cell membrane, depleting intracellular ATP14, and changing the P-glycoprotein drug efflux pump in multidrug resistant (MDR) cells[15,16,17]. Colon cancer metastasis, low dose of 5-Fu produces fewer adverse reactions, it is difficult to achieve an ideal treatment effect. High doses of 5-Fu therapy that can effectively inhibit the development of colon cancer, which always leads to more adverse reactions and chemotherapy resistance. We considered to combine 5-Fu and pluronic, trying to make 5-Fu produce strong pesticide effect at lower dose
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