ArticleOncotarget2018
Over-activation of AKT signaling leading to 5-Fluorouracil resistance in SNU-C5/5-FU cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Multifactorial mechanisms of 5-fluorouracil-induced cardiotoxicity and the cardioprotective role of gallic acid.Molecular biology reports · 2026Article
- Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation.Journal of the Egyptian National Cancer Institute · 2025Article
- SMAD4 inhibits glycolysis in ovarian cancer through PI3K/AKT/HK2 signaling pathway by activating ARHGAP10.Cancer reports (Hoboken, N.J.) · 2024Article
- Gemcitabine resistance in non-small cell lung cancer is mediated through activation of the PI3K/AKT/NF-κB pathway and suppression of ERK signaling by reactive oxygen species.Journal of biochemical and molecular toxicology · 2023Article
- Increased soluble E‑cadherin of spheroid formation supplemented with fetal bovine serum in colorectal cancer cells.Oncology letters · 2023Article
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Preparation of Novel Pyrazolo[4,3-International journal of molecular sciences · 2022Article
- Article
- Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.Biology · 2021Review
- Article
- The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer.Non-coding RNA · 2021Review
- Potentiating activities of chrysin in the therapeutic efficacy of 5-fluorouracil in gastric cancer cells.Oncology letters · 2021Article
- Konjac glucomannan reverses multi-drug resistance of HepG2/5-FU cells by suppressing AKT signaling and increasing p53 expression.Oncology letters · 2020Article
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- Article
- JTC-801 inhibits the proliferation and metastasis of the Hep G2 hepatoblastoma cell line by regulating the phosphatidylinositol 3-kinase/protein kinase B signalling pathway.Oncology letters · 2019Article
- Targeting Akt by SC66 triggers GSK-3β mediated apoptosis in colon cancer therapy.Cancer cell international · 2019Article
- Article
- Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer.Journal of oncology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here, we investigated whether over-activation of AKT pathway is important in the resistance to 5-fluorouracil (5-FU) in SNU-C5/5-FU cells, 5-FU-resistant human colon cancer cells. When compared to wild type SNU-C5 cells (WT), SNU-C5/5-FU cells showed over-activation of PI3K/AKT pathway, like increased phosphorylation of AKT, mTOR, and GSK-3β, nuclear localization of β-catenin, and decreased E-cadherin. Moreover, E-cadherin level was down-regulated in recurrent colon cancer tissues compared to primary colon cancer tissues. Gene silencing of AKT1 or treatment of LY294002 (PI3 kinase inhibitor) increased E-cadherin, whereas decreased phospho-GSK-3β. LY294002 also reduced protein level of β-catenin with no influence on mRNA level. PTEN level was higher in SNU-C5/WT than SNU-C5/5-FU cells, whereas the loss of PETN in SNU-C5/WT cells induced characteristics of SNU-C5/5-FU cells. In SNU-C5/5-FU cells, NF-κB signaling was activated, along with the overexpression of COX-2 and stabilization of survivin. However, increased COX-2 contributed to the stabilization of survivin, which directly interacts with cytoplasmic procaspase-3, while the inhibition of AKT reduced this cascade. We finally confirmed that combination treatment with 5-FU and LY294002 or Vioxx could induce apoptosis in SNU-C5/5-FU cells. These data suggest that inhibition of AKT activation may overcome 5-FU-resistance in SNU-C5/5-FU cells. These findings provide evidence that over-activation of AKT is crucial for the acquisition of resistance to anticancer drugs and AKT pathway could be a therapeutic target for cancer treatment.
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