title: Cooperative inhibitory effect of sinomenine combined with 5-fluorouracil on esophageal carcinoma.
abstract: OBJECTIVE
  To investigate the inhibitory effects of sinomenine (SIN) combined with 5-fluorouracil (5-FU) on esophageal carcinoma in vitro and in vivo.
  
  
  METHODS
  Esophageal carcinoma (Eca-109) cells were cultured in DMEM. The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8 dye in living cells. Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis. Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN at 25 mg/kg and 5-FU at 12 mg/kg every 3 d, either combined or alone, was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.
  
  
  RESULTS
  SIN and 5-FU, both in combination and individually, significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis. Furthermore, the combined effects were greater than those of the individual agents (P < 0.05). Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control (P < 0.05). The up-regulation of Bax and down-regulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway. SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo, and the combined inhibition rate was even higher (P < 0.05). During the course of chemotherapy, no obvious side effects were observed in the liver or kidneys.
  
  
  CONCLUSIONS
  The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds, and the drug combination did not increase the side effects of chemotherapy.
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Zi-Rong
authors.initials: ZR
authors.lastname: Yang
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dong
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Guo
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Jing Wang, Zi-Rong Yang, Wei-Guo Dong, Ji-Xiang Zhang, Xu-Feng Guo, Jia Song, Shi Qiu, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009019:Morphinans / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D009019:Morphinans; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C009271:sinomenine; D005472:Fluorouracil
keywords: 5-Fluorouracil; Chemotherapy; Esophageal carcinoma; Sinomenine