TY - JOUR T1 - Investigation into Enhancing Capecitabine Efficacy in Colorectal Cancer by Inhibiting Focal Adhesion Kinase Signaling JF - Anticancer Research JO - Anticancer Res SP - 4667 LP - 4676 DO - 10.21873/anticanres.12772 VL - 38 IS - 8 AU - JAE JUN SIM AU - MIN HEE PARK AU - JEONG-HEUM BAEK AU - HAEJUN LEE AU - KEUN-YEONG JEONG AU - HWAN MOOK KIM Y1 - 2018/08/01 UR - http://ar.iiarjournals.org/content/38/8/4667.abstract N2 - Background/Aim: Capecitabine is a pro-drug of 5-fluorouracil (5-FU), and is an orally available chemotherapeutic used to treat colorectal cancer (CRC). Recently, research has focused on improving its efficacy at lower doses in order to minimize its well-known toxicities. In this study, we investigated the possibility of improving the antitumor effect of capecitabine against CRC by destabilizing focal adhesion kinase (FAK) signaling. Materials and Methods: Optimal dosages for capecitabine and lactate calcium salt (LCS) were determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. The viability of CRC cells was investigated by MTT and clonogenic assays after single or combination treatment with capecitabine and LCS. Western blot analyses were used to determine changes in the expression of components of the FAK and AKT signaling cascade, and this information was used to elucidate the underlying mechanism. A xenograft model was established to evaluate the antitumor efficacy of the combination treatment, as well as its necrotic effect and organ toxicity. Results: The addition of LCS to capecitabine treatment led to an increase in the proteolysis of the FAK signaling cascade components, including SRC proto-oncogene, non-receptor tyrosine kinase; AKT serine/threonine kinase 1; and nuclear factor-kappa B, resulting in a decrease in the viability and clonogenic ability of CRC cells. In vivo antitumor efficacy, including tumor necrosis, was significantly increased with the combination treatment relative to both single treatments, and no organ toxicity was found in any experimental group. Conclusion: The addition of LCS increased the anticancer efficacy of capecitabine at a lower dose than is currently used in human patients. ER -