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Article

Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand

  • Authors:
    • Hui Chen
    • Liang‑Qing Li
    • Dun Pan
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
  • Pages: 3732-3736
    |
    Published online on: October 15, 2015
       https://doi.org/10.3892/ol.2015.3807
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Abstract

The aim of the present study was to evaluate the effect of geldanamycin (GA) on the treatment of human gastric carcinomas and to investigate the molecular mechanism that provides the basis for the combination of GA with the tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) induction strategy. The expression of target proteins at the mRNA level was determined using reverse transcription‑polymerase chain reaction (RT‑PCR), and apoptosis was evaluated with the terminal deoxynucleotidyl transferase mediated digoxigenin‑dUTP nick‑end labeling and Annexin V/propidium iodide (PI) staining methods. Phosphorylation of targeted kinases was studied using immunocytochemistry methods, and malignant phenotypes were studied using in vitro assays. GA treatment inhibits proliferation, migration and invasion, and induces apoptosis in human gastric cancer SGC‑7901 cells, most likely by decreasing the expression of B‑RAF and by phosphorylation of protein kinase B (AKT) and ERK. The inhibitory role of AKT in TRAIL regulation holds considerable potential for achieving a synergic effect in clinical therapy, using a combination of GA treatment and TRAIL induction. The present study provides a basis for the future application of heat shock protein 90 (Hsp90) inhibitors, such as GA, in the clinical treatment of gastric cancer, particularly in combination therapies with TRAIL inducers.
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Copy and paste a formatted citation
Spandidos Publications style
Chen H, Li LQ and Pan D: Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand. Oncol Lett 10: 3732-3736, 2015.
APA
Chen, H., Li, L., & Pan, D. (2015). Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand. Oncology Letters, 10, 3732-3736. https://doi.org/10.3892/ol.2015.3807
MLA
Chen, H., Li, L., Pan, D."Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand". Oncology Letters 10.6 (2015): 3732-3736.
Chicago
Chen, H., Li, L., Pan, D."Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand". Oncology Letters 10, no. 6 (2015): 3732-3736. https://doi.org/10.3892/ol.2015.3807
Copy and paste a formatted citation
x
Spandidos Publications style
Chen H, Li LQ and Pan D: Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand. Oncol Lett 10: 3732-3736, 2015.
APA
Chen, H., Li, L., & Pan, D. (2015). Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand. Oncology Letters, 10, 3732-3736. https://doi.org/10.3892/ol.2015.3807
MLA
Chen, H., Li, L., Pan, D."Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand". Oncology Letters 10.6 (2015): 3732-3736.
Chicago
Chen, H., Li, L., Pan, D."Geldanamycin induces apoptosis in human gastric carcinomas by affecting multiple oncogenic kinases that have synergic effects with TNF‑related apoptosis‑inducing ligand". Oncology Letters 10, no. 6 (2015): 3732-3736. https://doi.org/10.3892/ol.2015.3807
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