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Int. J. Mol. Sci. 2017, 18(11), 2363; doi:10.3390/ijms18112363

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

1
Department of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung 833, Taiwan
2
Center for General Education, National Formosa University, Yunlin 632, Taiwan
3
Department of Wood Based Materials and Design, National Chiayi University, Chiayi 600, Taiwan
4
Department of Medical Research and Development, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 613, Taiwan
5
Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan
6
Department of Pathology, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 600, Taiwan
7
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
8
Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
*
Author to whom correspondence should be addressed.
Received: 23 October 2017 / Revised: 6 November 2017 / Accepted: 6 November 2017 / Published: 8 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: 5-fluorouracil; AICAR; AMP-activated protein kinase; colorectal cancer; X-ray repair cross complementing group 1 5-fluorouracil; AICAR; AMP-activated protein kinase; colorectal cancer; X-ray repair cross complementing group 1
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MDPI and ACS Style

Lee, K.-C.; Lin, C.-T.; Chang, S.-F.; Chen, C.-N.; Liu, J.-L.; Huang, W.-S. 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. Int. J. Mol. Sci. 2017, 18, 2363.

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