Document Detail


Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells.
MedLine Citation:
PMID:  17439729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU) anticancer functions and its mechanisms in the human esophageal cancer cell line (Eca 109) and human colonic cancer cell line (Ls-174-t). METHODS: The effect of insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle distribution of both cell lines was analyzed by flow cytometry. Western blot assay was used to assess the expression of caspase-3 and thymidylate synthase (TS). Apoptosis was detected by flow cytometry, DNA fragmentation assay, and terminal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western blot analysis. RESULTS: We found that insulin enhanced the inhibitory effect of 5- FU on cell proliferation when Eca 109 cells and Ls-174-t cells were pretreated with insulin for the appropriate time. Insulin increased the cell number of the S phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor cells and upregulated the expression of cleaved caspase-3 compared with 5-FU treatment. Moreover, insulin/5-FU treatment induced the changes of free TS and the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t cells. CONCLUSION: These data suggest that insulin enhances anticancer functions of 5- FU when it is treated before 5-FU for the appropriate time in human esophageal and colonic cancer cell lines.
Authors:
Ke Zou; Ji-Hang Ju; Hong Xie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  28     ISSN:  1671-4083     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-18     Completed Date:  2009-04-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  China    
Other Details:
Languages:  eng     Pagination:  721-30     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols
Apoptosis / physiology
Cell Cycle / physiology
Cell Line, Tumor
Colonic Neoplasms / drug therapy*,  metabolism
Esophageal Neoplasms / drug therapy*,  metabolism
Fluorouracil / metabolism,  therapeutic use*
Humans
Insulin / therapeutic use*
Thymidylate Synthase / metabolism
Chemical
Reg. No./Substance:
11061-68-0/Insulin; 51-21-8/Fluorouracil; EC 2.1.1.45/Thymidylate Synthase

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