Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2047-2057
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2047
Impact of high glucose on metastasis of colon cancer cells
Cheng-Yao Lin, Chih-Hui Lee, Chien-Cheng Huang, Song-Tay Lee, How-Ran Guo, Shih-Bin Su
Cheng-Yao Lin, Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan
Cheng-Yao Lin, Department of Dental Laboratory Technology, Min-Hwei College of Health Care Management, Tainan 736, Taiwan
Chih-Hui Lee, Department of Public Health, National Cheng Kung University, Tainan 701, Taiwan
Chien-Cheng Huang, Department of Emergency Medicine, Chi-Mei Medical Center, Tainan 710, Taiwan
Chien-Cheng Huang, Department of Child Care and Education, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan
Song-Tay Lee, Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan
How-Ran Guo, Department of Environmental and Occupational Health, National Cheng Kung University, Tainan 701, Taiwan
Shih-Bin Su, Department of Occupational Medicine, Chi-Mei Medical Center, Tainan 710, Taiwan
Shih-Bin Su, Department of Medical Research, Chi Mei Medical Center, Liouying, Tainan 736, Taiwan
Author contributions: Lin CY and Su SB designed the research; Lin CY, Lee ST and Huang CC performed the research; Lin CY, Lee CH, Huang CC and Guo HR contributed analyzed data; and Lin CY, Lee CH and Su SB wrote the paper.
Supported by Chi-Mei Medical Center Grant, No. CMFHR10252
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shih-Bin Su, MD, PhD, Department of Occupational Medicine, Chi-Mei Medical Center, 901 Zhonghua Road, Yung-Kang District, Tainan 710, Taiwan. 880601@mail.chimei.org.tw
Telephone: +886-6-2812811 Fax: +886-6-2816161
Received: June 23, 2014
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
Abstract

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.

Keywords: Colorectal cancer, Glucose, Signal transducer and activator of transcription 3, Matrix metalloproteinase-9, Metastasis

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.