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

Abstract

PurposeColorectal 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).MethodsMultiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, western blotting and flow cytometry.ResultsWe 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.ConclusionThese 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.

Epigenetic targeting of autophagy for cancer: DNA and RNA methylation

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The progress of protein synthesis factors eIFs, eEFs and eRFs in inflammatory bowel disease and colorectal cancer pathogenesis

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