title: Synergistic effects of puerarin combined with 5-fluorouracil on esophageal cancer.
abstract: Puerarin is an isoflavone derived from kudzu roots with a wide range of biological and medicinal properties. The aim of the present study was to investigate the inhibitive effects of puerarin combined with 5‑fluorouracil (5‑FU) on Eca‑109 esophageal cancer cells in vitro and in vivo. Inhibitive effects of the treatments on Eca‑109 cells were detected by cell counting kit‑8, Hoechst 33258 staining and flow cytometry. A tumor xenograft model was established in nude mice. Puerarin and 5‑FU, administered either in combination or individually, were injected into mice and the inhibitive effects along with any side effects were observed. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Puerarin and 5‑FU, administered as combined treatment or individual drugs, significantly inhibited proliferation and induced marked apoptosis. The mean growth inhibition rate (± standard deviation) reached 87.27±5.37% and the apoptotic rate at 48 h reached 36.18±1.24% in the combined treatment group. The percentages of apoptotic cells induced by puerarin and 5‑FU (combined or alone) were significantly higher than those of the control group (P<0.05). Puerarin or 5‑FU alone significantly inhibited the growth of xenograft tumors in comparison to the control group (P<0.05), with inhibition rates of 76.93 and 72.21%, respectively. The drugs combined exhibited a significantly greater effect than either drug alone (P<0.05), with the tumor inhibition rate reaching 89.06%. During the course of chemotherapy, no evident side effects were observed. The results suggested that the combined inhibitive effects of puerarin and 5‑FU were greater than the effects of the agents used individually. In addition, puerarin combined with 5‑FU exhibited synergistic effects at lower concentrations and promoted apoptosis, but did not increase the side effects of chemotherapy, which indicated that puerarin may be a safe and effective chemosensitive agent in the treatment of human esophageal cancer.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zi-Rong
authors.initials: ZR
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dong
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D007529:Isoflavones; D005472:Fluorouracil; C033607:puerarin