Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells
Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the act...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2017-11-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/18/11/2363 |
id |
doaj-af19078ae90a45b9aa376547394159db |
---|---|
record_format |
Article |
spelling |
doaj-af19078ae90a45b9aa376547394159db2020-11-25T00:22:25ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-11-011811236310.3390/ijms18112363ijms18112363Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer CellsKo-Chao Lee0Chien-Tsong Lin1Shun-Fu Chang2Cheng-Nan Chen3Jing-Lan Liu4Wen-Shih Huang5Department of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung 833, TaiwanCenter for General Education, National Formosa University, Yunlin 632, TaiwanDepartment of Medical Research and Development, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 613, TaiwanDepartment of Biochemical Science and Technology, National Chiayi University, Chiayi 600, TaiwanDepartment of Pathology, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 600, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanColorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms. Human HCT-116 colorectal cells were used in this study. It was shown that 5-FU increases the XRCC1 expression in HCT-116 cells and then affects the cell survival through CXCR4/Akt signaling. Moreover, 5-FU combined with AICAR further result in more survival inhibition in HCT-116 cells, accompanied with reduced CXCR4/Akt signaling activity and XRCC1 expression. These results elucidate the role and mechanism of XRCC1 in the drug resistance of HCT-116 cells to 5-FU. We also demonstrate the synergistic inhibitory effect of AMPK on 5-FU-inhibited HCT-116 cell survival under the 5-FU and AICAR co-treatment. Thus, our findings may provide a new notion for the future drug regimen incorporating 5-FU and AMPK agonists for the CRC treatment.https://www.mdpi.com/1422-0067/18/11/23635-fluorouracilAICARAMP-activated protein kinasecolorectal cancerX-ray repair cross complementing group 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ko-Chao Lee Chien-Tsong Lin Shun-Fu Chang Cheng-Nan Chen Jing-Lan Liu Wen-Shih Huang |
spellingShingle |
Ko-Chao Lee Chien-Tsong Lin Shun-Fu Chang Cheng-Nan Chen Jing-Lan Liu Wen-Shih Huang Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells International Journal of Molecular Sciences 5-fluorouracil AICAR AMP-activated protein kinase colorectal cancer X-ray repair cross complementing group 1 |
author_facet |
Ko-Chao Lee Chien-Tsong Lin Shun-Fu Chang Cheng-Nan Chen Jing-Lan Liu Wen-Shih Huang |
author_sort |
Ko-Chao Lee |
title |
Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells |
title_short |
Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells |
title_full |
Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells |
title_fullStr |
Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells |
title_full_unstemmed |
Effect of AICAR and 5-Fluorouracil on X-ray Repair, Cross-Complementing Group 1 Expression, and Consequent Cytotoxicity Regulation in Human HCT-116 Colorectal Cancer Cells |
title_sort |
effect of aicar and 5-fluorouracil on x-ray repair, cross-complementing group 1 expression, and consequent cytotoxicity regulation in human hct-116 colorectal cancer cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-11-01 |
description |
Colorectal cancer (CRC) is one of the leading causes of cancer mortality and 5-Fluorouracil (5-FU) is the most common chemotherapy agent of CRC. A high level of X-ray repair cross complementing group 1 (XRCC1) in cancer cells has been associated with the drug resistance occurrence. Moreover, the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been indicated to regulate the cancer cell survival. Thus, this study was aimed to examine whether XRCC1 plays a role in the 5-FU/AMPK agonist (AICAR)-induced cytotoxic effect on CRC and the underlying mechanisms. Human HCT-116 colorectal cells were used in this study. It was shown that 5-FU increases the XRCC1 expression in HCT-116 cells and then affects the cell survival through CXCR4/Akt signaling. Moreover, 5-FU combined with AICAR further result in more survival inhibition in HCT-116 cells, accompanied with reduced CXCR4/Akt signaling activity and XRCC1 expression. These results elucidate the role and mechanism of XRCC1 in the drug resistance of HCT-116 cells to 5-FU. We also demonstrate the synergistic inhibitory effect of AMPK on 5-FU-inhibited HCT-116 cell survival under the 5-FU and AICAR co-treatment. Thus, our findings may provide a new notion for the future drug regimen incorporating 5-FU and AMPK agonists for the CRC treatment. |
topic |
5-fluorouracil AICAR AMP-activated protein kinase colorectal cancer X-ray repair cross complementing group 1 |
url |
https://www.mdpi.com/1422-0067/18/11/2363 |
work_keys_str_mv |
AT kochaolee effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells AT chientsonglin effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells AT shunfuchang effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells AT chengnanchen effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells AT jinglanliu effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells AT wenshihhuang effectofaicarand5fluorouracilonxrayrepaircrosscomplementinggroup1expressionandconsequentcytotoxicityregulationinhumanhct116colorectalcancercells |
_version_ |
1725359931846033408 |