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Eukaryotic translation initiation factor 3 subunit G (EI F3G) resensitized HC T116/5-Fu to 5-fluorouracil (5-Fu) via inhibition of MRP and MDR1

Authors Yang C, Liu X, Li C, Li S, Du W, Yang D

Received 12 April 2018

Accepted for publication 12 June 2018

Published 31 August 2018 Volume 2018:11 Pages 5315—5324

DOI https://doi.org/10.2147/OTT.S170854

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai


Chenggang Yang,1 Xin Liu,1 Chaobin Li,2 Shuangjing Li,3 Wenfeng Du,1 Daogui Yang1

1Department of Gastrointestinal Surgery, 2Department of Gastroenterology, 3Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, China

Purpose: Colorectal cancer (CRC) has become a predominant cancer and accounts for approximately 10% of cancer-related mortality. Drug resistance still remains a priority mortality factor for patients due to no available therapeutic alternatives. The purpose of the present study was to investigate the underlying molecular mechanisms how eukaryotic translation initiation factor 3 subunit G (EIF3G) resensitized 5-Fu-resistant human CRC cells (HCT116/5-Fu) to 5-fluorouracil (5-Fu).
Methods: Multiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, western blotting and flow cytometry.
Results: We found that EIF3G is highly expressed at RNA and protein levels in HCT116/5-Fu cells compared with HCT116 cells using quantitative real-time polymerase chain reaction and Western blot analysis. In addition, silencing EIF3G enhanced 5-Fu-induced apoptosis in HCT116/5-Fu cells. Moreover, EIF3G silencing decreased the activity of the drug-related proteins MDR1 and MRP levels in HCT116/5-Fu cells. Finally, the xenograft tumor model further confirmed that EIF3G resensitized HCT116/5-Fu tumors to 5-Fu. We observed that EIF3G silencing followed by 5-Fu administration had a synergistic interaction effect on HCT116/5-Fu in vitro and in vivo.
Conclusion: These findings demonstrate that EIF3G is a targetable regulator of chemoresistance in CRC, and inhibiting EIF3G in combination with 5-Fu might be a potential therapeutic strategy for colon cancer.

Keywords: EIF3G, colorectal cancer, 5-fluorouracil, drug resistance, MDR1, MRP

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