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Abstract
5-Fluorouracil (5-FU) over-use has led to an urgent need for alternative treatment regimens, such as a lower concentration of the drug because of its toxic effects. The aim of this study was to investigate the possibility of improving the antitumor effect of 5-FU without toxicity by targeting primary colorectal cancer (CRC) with sustained calcium supplementation. The viability of CRC cells was determined after treatment of 5-FU, lactate calcium salt (CaLac), or the combination of te two. Western blot analysis for the focal adhesion kinase (FAK) signaling cascade was performed to investigate the underlying mechanism. A xenograft model was established to evaluate antitumor efficacy of each treatment, and the necrotic effect was also observed in tumor tissues. By the combined treatment, proteolysis of FAK signaling cascade, was mediated by sustained calcium supplementation resulting in further decrease in the clonogenicity of CRC cells. The in vivo anticancer efficacy including tumor necrosis was significantly increased by the combination treatment compared to single treatment of with 5-FU. Sustained calcium supplementation was able to enhance the potency of 5-FU targeting the primary CRC.
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