title: Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460.
abstract: The present study investigated the ability of carboplatin and paclitaxel to sensitize human non-small-cell lung cancer (NSCLC) cells to carbon-ion beam irradiation. NSCLC H460 cells treated with carboplatin or paclitaxel were irradiated with X-rays or carbon-ion beams, and radiosensitivity was evaluated by clonogenic survival assay. Cell proliferation was determined by counting the number of viable cells using Trypan blue. Apoptosis and senescence were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and senescence-associated β-galactosidase (SA-β-gal) staining, respectively. The expression of cleaved caspase-3, Bax, p53 and p21 was analyzed by western blotting. Clonogenic survival assays demonstrated a synergistic radiosensitizing effect of carboplatin and paclitaxel with carbon-ion beams; the sensitizer enhancement ratios (SERs) at the dose giving a 10% survival fraction (D10) were 1.21 and 1.22, respectively. Similarly, carboplatin and paclitaxel showed a radiosensitizing effect with X-rays; the SERs were 1.41 and 1.29, respectively. Cell proliferation assays validated the radiosensitizing effect of carboplatin and paclitaxel with both carbon-ion beam and X-ray irradiation. Carboplatin and paclitaxel treatment combined with carbon-ion beams increased TUNEL-positive cells and the expression of cleaved caspase-3 and Bax, indicating the enhancement of apoptosis. The combined treatment also increased SA-β-gal-positive cells and the expression of p53 and p21, indicating the enhancement of senescence. In summary, carboplatin and paclitaxel radiosensitized H460 cells to carbon-ion beam irradiation by enhancing irradiation-induced apoptosis and senescence.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan snoda@gunma-u.ac.jp.
authors.forename: Shin-ei
authors.initials: SE
authors.lastname: Noda
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, Gunma, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Gunma University Heavy Ion Medical Center, Gunma, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Murata
authors.affiliation: Gunma University Heavy Ion Medical Center, Gunma, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Musha
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Gunma University Heavy Ion Medical Center, Gunma, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Department of Radiology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan Gunma University Heavy Ion Medical Center, Gunma, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002244:Carbon / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002244:Carbon; D016190:Carboplatin; D017239:Paclitaxel
keywords: carbon-ion beams; carboplatin; lung cancer; paclitaxel; radiosensitization