The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells
| Autor: | Ryuichi Okayasu, Akira Fujimori, Hirokazu Hirakawa, Hiroshi Fujisawa, Aya Masaoka, Ryoichi Hirayama, Miho Noguchi, Momoko Takahashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Lung Neoplasms DNA Repair DNA repair Cell Survival Lactams Macrocyclic Mice Nude Antineoplastic Agents Heavy Ion Radiotherapy Hsp90 inhibitor In vivo Cell Line Tumor medicine Benzoquinones Animals Humans Radiology Nuclear Medicine and imaging HSP90 Heat-Shock Proteins Lung cancer heavy ions Cancer Biology Mice Inbred BALB C 17AAG biology Cell cycle medicine.disease Hsp90 Combined Modality Therapy In vitro Tumor Burden lung cancer Oncology Cancer research biology.protein Rad51 Recombinase Homologous recombination |
| Zdroj: | Cancer Medicine |
| ISSN: | 2045-7634 |
| Popis: | Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors. |
| Databáze: | OpenAIRE |
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