Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2047
Peer-review started: June 23, 2014
First decision: June 23, 2014
Revised: August 6, 2014
Accepted: November 18, 2014
Article in press: November 19, 2014
Published online: February 21, 2015
Processing time: 233 Days and 10.4 Hours
AIM: 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).
CONCLUSION: 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.
Core tip: It has been known from several epidemiological reports that colorectal cancer patients with comorbid diabetes have poor outcomes. The high glucose status in diabetes patients may play an important role in this process, but the possible mechanism is unclear. Our study reveals that glucose can promote colorectal cell migration and invasion, and the signal transducer and activator of transcription 3 induced matrix metalloproteinase-9 expression is involved in this process.