title: Longitudinal time-dependent effects of irradiation on multidrug resistance in a non-small lung cancer cell line.
abstract: Multidrug resistance (MDR) in cancer is known to decrease the therapeutic efficacy of chemotherapy. The effects of irradiation on MDR in cancer cells remain unclear. Tc-99m methoxyisobutylisonitrile (MIBI) exhibits the same ATP-binding cassette (ABC) transporter kinetics as the chemotherapeutic compound doxorubicin. In this study, we investigated the synergistic effects of chemotherapeutics and irradiation [0 Gy: C (control) group; 3, 6, 9, 12 Gy: I (irradiation) group] in the human non-small lung cancer cell line H1299 exhibiting MDR, on MIBI and doxorubicin ABC transporter kinetics, in vitro and in vivo, respectively. In vitro, inhibition of H1299 cell proliferation by irradiation was found to be irradiation dose dependent. The degree and duration of MDR inhibition in vitro in H1299 were also dose dependent. In the cells of both the C group and 3-Gy I group, no significant difference of MIBI accumulation was observed. In the 6-Gy I group, a higher MIBI accumulation was observed at only 7 days after irradiation relative to the C group. A higher MIBI accumulation in the 9- and 12-Gy I groups with a significant difference from the C group was observed at 4 to 14 days after irradiation. A significant negative correlation between intracellular MIBI accumulation and cell replication was found. In vivo, high accumulation and retention of doxorubicin were observed in irradiated tumors in the H1299 xenograft mice group at 4 to 14 days after 9-Gy irradiation compared with the control mice group. These results provide evidence for a synergistic effect of concurrent chemotherapy and radiotherapy.
authors.affiliation: Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan. kohnoy@hirakata.kmu.ac.jp.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kono
authors.affiliation: Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Utsunomiya
authors.affiliation: Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Tanigawa
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi