Impact of high glucose on metastasis of colon cancer cells

作者：Lin Cheng Yao; Lee Chih Hui; Huang Chien Cheng; Lee Song Tay; Guo How Ran; Su Shih Bin^*

来源：World Journal of Gastroenterology, 2015, 21(7): 2047-2057.

DOI：10.3748/wjg.v21.i7.2047

• Colorectal cancer
• Glucose
• Signal transducer and activator of transcription 3
• Matrix metalloproteinase-9
• Metastasis

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.

• 出版日期2015-2-21