title: Icariin-mediated inhibition of NF-κB activity enhances the in vitro and in vivo antitumour effect of 5-fluorouracil in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Colorectal Surgery, Cancer Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: De-Bing
authors.initials: DB
authors.lastname: Shi
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Li
authors.forename: Hong-Tu
authors.initials: HT
authors.lastname: Zheng
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Cai
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Peng
authors.forename: Wei-Lie
authors.initials: WL
authors.lastname: Gu
authors.forename: Zu-Qing
authors.initials: ZQ
authors.lastname: Guan
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: San-Jun
authors.initials: SJ
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D016328:NF-kappa B; D005472:Fluorouracil; C056599:icariin