Department of Biochemistry, Panjab University, Chandigarh, 160014, India.
Cancer Chemother Pharmacol. 2014 Aug;74(2):309-22. doi: 10.1007/s00280-014-2497-6. Epub 2014 Jun 11.
5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model.
The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney.
In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs.
The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.
5-氟尿嘧啶（5-FU）用于治疗结直肠癌，但治疗反应率低，副作用严重。最近，富含 n-3 多不饱和脂肪酸的鱼油（FO）已被优先用于化学增敏肿瘤细胞对抗癌药物的作用。因此，本研究旨在评估 5-FU 联合 FO 对 1,2-二甲基肼二盐酸盐/葡聚糖硫酸钠（DMH/DSS）诱导的结肠癌模型的化疗疗效和毒性特征。
通过评估存活率、肿瘤负担、体积、血清唾液酸水平、细胞角蛋白 19（CK19）表达和细胞增殖指数（如细胞周期进展）来分析 5-FU 联合 FO 的治疗效果。毒理学方面通过与脾脏、胃肠道、肝脏和肾脏相关的标准功能和结构参数进行评估。
在本研究中，5-FU 联合 FO 提高了致癌物处理动物的存活率。5-FU 和 FO 的协同作用也反映在 DMH/DSS 模型中肿瘤生长和血清唾液酸水平的显著抑制上。此外，联合剂量显著增强了细胞周期进展的抑制，如 CK19 表达所示。此外，FO 改善了 5-FU 引起的血液学抑制、胃肠道、肝和肾毒性，这些器官的结构和功能改变得到了显著改善。
FO 的补充可能是增加 5-FU 治疗潜力和减轻其副作用的有前途的选择。
