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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Investigation into Enhancing Capecitabine Efficacy in Colorectal Cancer by Inhibiting Focal Adhesion Kinase Signaling
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Investigation into Enhancing Capecitabine Efficacy in Colorectal Cancer by Inhibiting Focal Adhesion Kinase Signaling

机译：通过抑制局灶性粘附激酶信号传导来调查结肠直肠癌中的Capecitabine疗效

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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.
机译：背景/目的：Capecitabine是5-氟尿嘧啶（5-FU）的药物，是一种原口可用的化学治疗剂，用于治疗结肠直肠癌（CRC）。最近，研究专注于改善较低剂量的疗效，以最大限度地减少其众所周知的毒性。在这项研究中，我们调查了通过稳定局灶性粘附激酶（FAK）信号传导来改善Capecitabine对CRC的抗肿瘤效应的可能性。材料和方法：使用3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-四唑溴铵MTT测定法测定Capecitabine和乳酸钙盐（LCS）的最佳剂量。用Capecitabine和LCs的单一或组合处理后，通过MTT和克隆核测定研究CRC细胞的活力。 Western印迹分析用于确定FAK和AKT信号级联的组件表达的变化，并且该信息用于阐明潜在机制。建立了异种移植模型，以评估组合治疗的抗肿瘤效果，以及其坏死效应和器官毒性。结果：将LCS添加到Capecitabine治疗中导致FAK信号级联组分的蛋白水解增加，包括SRC原癌基因，非受体酪氨酸激酶; AKT丝氨酸/苏氨酸激酶1;和核因子-Kappa B，导致CRC细胞的活力和克隆灭绝能力的降低。在体内抗肿瘤效果中，包括肿瘤坏死，随着单一处理的组合治疗明显增加，任何实验组都没有发现器官毒性。结论：LCS的添加增加了氯硝滨的抗癌功效，比人类患者目前用于较低的剂量。

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