IMDEA-Food Institute, CEI UAM+CSIC, C/Faraday 7, 28049 Madrid, Spain.
Pharmacol Res. 2013 Jun;72:61-8. doi: 10.1016/j.phrs.2013.03.010. Epub 2013 Apr 1.
5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal cancer. However, resistance to this drug is relatively frequent, and new strategies to overcome it are urgently needed. The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy useful for colon cancer patients. This extract has been recognized as a healthy component by the European Food Safety Authority (EFSA). The effects of SFRE both alone and in combination with 5-FU were evaluated in different human colon cancer cells in terms of cell viability, cytotoxicity, and cell transformation. Additionally, colon cancer cells resistant to 5-FU were used to assay the effects of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5-FU. Our results show that SFRE displays dose-dependent antitumor activities and exerts a synergistic effect in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU-resistant cells to the therapeutic activity of this drug, constituting a beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene expression analysis indicates that the enhancement of the effect of 5-FU by SFRE might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU resistance.
5-氟尿嘧啶（5-FU）是结直肠癌中最常用的化疗药物。然而，这种药物的耐药性相对较高，迫切需要新的策略来克服它。本工作旨在确定迷迭香超临界流体提取物（SFRE）单独或与 5-FU 联合作为结肠癌患者辅助治疗的潜在用途的抗肿瘤特性。这种提取物已被欧洲食品安全局（EFSA）确认为健康成分。SFRE 单独或与 5-FU 联合对不同的人结肠癌细胞的细胞活力、细胞毒性和细胞转化进行了评估。此外，还使用对 5-FU 耐药的结肠癌细胞来检测 SFRE 对耐药性的影响。最后，通过 qRT-PCR 确定 SFRE 增强 5-FU 作用的机制。我们的结果表明，SFRE 表现出剂量依赖性的抗肿瘤活性，并与 5-FU 对结肠癌细胞产生协同作用。此外，SFRE 使 5-FU 耐药细胞对该药物的治疗活性敏感，成为对 5-FU 敏感和耐药肿瘤细胞都有效的有益药物。基因表达分析表明，SFRE 增强 5-FU 作用的机制可能是通过下调与 5-FU 耐药相关的 TYMS 和 TK1 酶来解释的。
