Shi De-Bing, Li Xin-Xiang, Zheng Hong-Tu, Li Da-Wei, Cai Guo-Xiang, Peng Jun-Jie, Gu Wei-Lie, Guan Zu-Qing, Xu Ye, Cai San-Jun
Department of Colorectal Surgery, Cancer Hospital, Fudan University, Shanghai, 200032, China.
Cell Biochem Biophys. 2014 Jul;69(3):523-30. doi: 10.1007/s12013-014-9827-5.
Colorectal cancer (CRC) is an aggressive malignancy that has a poor prognosis. 5-Fluorouracil (5-FU) is a first line chemotherapeutic medication used in the treatment of gallbladder cancer; however, the efficacy is below satisfactory. Icariin is a natural compound that is conventionally reported to have activity against a variety of cancers. This study was carried out to investigate the anti-cancer effect of icariin in CRC cells and to determine whether the compound can enhance the antitumour activity of 5-FU. Cell proliferation and apoptosis were measured using an MTT assay and flow cytometry, respectively. The activity of transcription factor NF-κB was determined by EMSA method. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The in vivo antitumour effect of combination treatment with icariin and 5-FU on CRC was also assessed using a murine model of CRC. Icariin sensitized the CRC cells to 5-FU both in vitro and in vivo. The antitumour activity of icariin and its potentiating effect on the antitumour activity of 5-FU implicated the suppression of NF-κB activity and consequent down-regulation of the gene products regulated by NF-κB. Our results showed that icariin, suppressed tumour growth and enhanced the antitumour activity of 5-FU in CRC by inhibiting NF-κB activity. Therefore, we suggest that combination of icariin with 5-FU might offer a therapeutic benefit to the patients with CRC; however, further studies are required to ascertain this proposition.
结直肠癌（CRC）是一种侵袭性恶性肿瘤，预后较差。5-氟尿嘧啶（5-FU）是用于治疗胆囊癌的一线化疗药物；然而，其疗效并不令人满意。淫羊藿苷是一种天然化合物，传统上报道其对多种癌症具有活性。本研究旨在探讨淫羊藿苷对CRC细胞的抗癌作用，并确定该化合物是否能增强5-FU的抗肿瘤活性。分别使用MTT法和流式细胞术检测细胞增殖和凋亡。通过电泳迁移率变动分析（EMSA）方法测定转录因子NF-κB的活性。通过蛋白质印迹法测定凋亡和增殖相关蛋白的表达。还使用CRC小鼠模型评估了淫羊藿苷和5-FU联合治疗对CRC的体内抗肿瘤作用。淫羊藿苷在体外和体内均使CRC细胞对5-FU敏感。淫羊藿苷的抗肿瘤活性及其对5-FU抗肿瘤活性的增强作用与NF-κB活性的抑制以及随后由NF-κB调节的基因产物的下调有关。我们的结果表明，淫羊藿苷通过抑制NF-κB活性抑制CRC肿瘤生长并增强5-FU的抗肿瘤活性。因此，我们认为淫羊藿苷与5-FU联合使用可能对CRC患者具有治疗益处；然而，需要进一步研究来确定这一观点。
