論文 - 詳細
| RRC ID | 42067 |
|---|---|
| 著者 | Machida H, Matsumoto Y, Shirai M, Kubota N. |
| タイトル | Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation. |
| ジャーナル | Int J Radiat Biol |
| Abstract |
PURPOSE:The effects of the heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA) were examined on the radiosensitivity and signal transduction pathways in human tumour cell lines. MATERIALS AND METHODS:Two human cell lines, SQ-5 and DLD-1, derived from lung carcinoma and colon adenocarcinoma, respectively, were incubated for 16 h at 37 degrees C in medium containing 0.2 microM GA. The cells were then irradiated with X-rays and incubated with GA for a further 8 h. Radiation sensitivity was determined by clonogenic assays and protein levels were examined by Western blotting. RESULTS:GA radiosensitized both cell lines, but potentiated X-ray sensitivity more in SQ-5 than in DLD-1 cells. It was found that GA depleted EGFR and ErbB-2 in DLD-1 cells and depleted only ErbB-2 in SQ-5 cells. GA also reduced the expression of Akt and phosphorylated Akt (pAkt) expression in SQ-5 cells. In addition, the ratio (%) of apoptotic cells and poly [ADP-ribose] polymerase cleavage increased in SQ-5 but not in DLD-1 cells after exposure to GA and X-ray irradiation. The findings suggest that GA enhances the radiation sensitivity of human tumour cells by inhibiting the EGFR signal transduction system and the Akt signalling pathway. CONCLUSION:Targeting Hsp90 with GA provides a promising experimental strategy for radiosensitization of carcinoma. |
| 巻・号 | 79(12) |
| ページ | 973-80 |
| 公開日 | 2003-12-1 |
| DOI | 10.1080/09553000310001626135 |
| PII | B0MA17VVB40N0X5J |
| PMID | 14713575 |
| MeSH | Adenocarcinoma / metabolism* Adenocarcinoma / pathology Apoptosis / drug effects Apoptosis / radiation effects Benzoquinones Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Line, Tumor / drug effects Cell Line, Tumor / metabolism Cell Line, Tumor / pathology Cell Line, Tumor / radiation effects Cell Survival / drug effects Cell Survival / radiation effects Colony-Forming Units Assay Dose-Response Relationship, Drug Dose-Response Relationship, Radiation ErbB Receptors / metabolism* HSP90 Heat-Shock Proteins / antagonists & inhibitors* Humans Lactams, Macrocyclic Protein Serine-Threonine Kinases* Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-akt Quinones / pharmacology* Radiation Dosage Radiation Tolerance / drug effects* Radiation-Sensitizing Agents / pharmacology* Signal Transduction / drug effects Signal Transduction / radiation effects X-Rays |
| IF | 2.368 |
| 引用数 | 56 |
| WOS 分野 | NUCLEAR SCIENCE & TECHNOLOGY RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | SQ-5(RCB0110) |