International journal of oncology, 2006-07, Vol.29 (1), p.249-253
2006
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- Autor(en) / Beteiligte
- Titel
- LY294002, an inhibitor of PI-3K, enhances heat sensitivity independently of p53 status in human lung cancer cells
- Ist Teil von
- International journal of oncology, 2006-07, Vol.29 (1), p.249-253
- Ort / Verlag
- Athens: Editorial Academy of the International Journal of Oncology
- Erscheinungsjahr
- 2006
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The aim of this study was to ascertain whether LY294002, an inhibitor of PI-3K, enhances heat sensitivity in human cancer cells regardless of their p53 status. Colony formation assays showed that LY294002 enhanced heat sensitivity in two human lung cancer cell lines; H1299/wild-type p53 (wtp53) and H1299/mutated p53 (mp53) cells. These cell lines have identical genetic backgrounds except for their p53 status. LY294002 suppressed the heat-induced accumulation of heat shock protein 27 (hsp27) and heat shock protein 72 (hsp72) in these cell lines. Heat-induced apoptosis was observed more frequently in H1299/wtp53 cells than in H1299/mp53 cells, and was enhanced by LY294002 in both cell lines. In addition, both the heat-induced phosphorylation of Akt and the accumulation of survivin were suppressed by LY294002. These results suggest that LY294002 inhibits anti-apoptosis signaling through hsp27 and hsp72 as well as cell survival signaling through Akt and survivin. LY294002 appears to be an attractive candidate for a p53-independent heat sensitizer in hyperthermic cancer therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1019-6439eISSN: 1791-2423DOI: 10.3892/ijo.29.1.249Titel-ID: cdi_proquest_miscellaneous_68074058
- Format
- –
- Schlagworte
- Apoptosis - drug effects, Biological and medical sciences, Cell Line, Tumor, Cell Survival - drug effects, Chromones - pharmacology, DNA - metabolism, DNA-Binding Proteins - metabolism, Heat Shock Transcription Factors, Heat-Shock Proteins - metabolism, Hot Temperature, HSP27 Heat-Shock Proteins, HSP72 Heat-Shock Proteins - genetics, HSP72 Heat-Shock Proteins - metabolism, Humans, Hyperthermia, Induced, Inhibitor of Apoptosis Proteins, Lung Neoplasms - enzymology, Lung Neoplasms - genetics, Lung Neoplasms - therapy, Medical sciences, Microtubule-Associated Proteins - metabolism, Morpholines - pharmacology, Mutation, Neoplasm Proteins - metabolism, Phosphatidylinositol 3-Kinases - antagonists & inhibitors, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation - drug effects, Pneumology, Protein Kinase Inhibitors - pharmacology, Proto-Oncogene Proteins c-akt - metabolism, Response Elements - genetics, Transcription Factors - metabolism, Transfection, Tumor Stem Cell Assay, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumors, Tumors of the respiratory system and mediastinum, Up-Regulation - drug effects