title: Impact of high glucose on metastasis of colon cancer cells.
abstract: OBJECTIVE
  To investigate the possible mechanism of how glucose promotes invasion and metastasis of colon cancer cells.
  
  
  METHODS
  CT-26 rat colorectal cancer cells were cultured in different concentrations of glucose environments (10, 20, and 30 mmol/L). Wound healing assay and transwell chamber invasion assay were utilized to test the migration and invasion, respectively. In order to understand the role of signal transducer and activator of transcription 3 (STAT3) in the process, STAT3 inhibitors, including Stattic (an STAT3 specific inhibitor) and small interfering RNA targeting STAT3, were used to block STAT3 function to evaluate their impact on CT-26 cell motion. To verify whether STAT3 and matrix metalloproteinase-9 (MMP-9) protein expression is associated with glucose-induced cell movement, Western blot was used to compare the differences in the expression of MMP-9 and STAT3 in cells incubated with and without STAT3 inhibitors in high glucose condition.
  
  
  RESULTS
  In both wound healing and invasion assays, the migration and invasion of CT-26 cells increased gradually with the increase in glucose concentration. However, the glucose-induced migration and invasion were obviously inhibited by STAT3 inhibitors (P<0.05). Similarly, in Western blot assessment, both MMP-9 and STAT3 expression increased under a high glucose environment and the highest expression was achieved when 30 mmol/L glucose was used. However, in cells treated with 30 mmol/L mannitol, either MMP-9 or STAT3 expression did not increase (P>0.05). When STAT3 inhibitors were added in the 30 mM glucose group, not only STAT3 but also MMP-9 expression decreased significantly (P<0.05).
  
  
  CONCLUSIONS
  Our study provides evidence that glucose can promote both migration and invasion of CT-26 cells, and that the STAT3-induced MMP-9 signal pathway is involved in this process.
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Cheng-Yao
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Chih-Hui
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Song-Tay
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: How-Ran
authors.initials: HR
authors.lastname: Guo
authors.affiliation: Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Shih-Bin
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D051381:Rats; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D005947:Glucose
keywords: Colorectal cancer; Glucose; Matrix metalloproteinase-9; Metastasis; Signal transducer and activator of transcription 3