Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells.
Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate vinorelbine-induced radiosensitization of human small cell lung cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization. A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by vinorelbine using different schedules combining exposure to both. The sensitizer enhancement ratios (SERs) at a cell survival level of 10% were 1.42+/-0.21 to 1.33+/-0.06, and 1.22+/-0.07 depending on schedule. Vinorelbine-induced radiosensitization did not depend on the schedule of the combined exposure. Flow cytometric analyses showed that the cells did not accumulate in the radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with vinorelbine and radiation. The results of an alkaline filter elution assay demonstrated that in the presence of vinorelbine at 1 n M radiation-induced DNA strand breaks were not completely repaired at 24 h postradiation. We conclude that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a possible mechanisms of vinorelbine-induced radiosensitization may at least in part be associated with impairment of DNA repair following radiation-induced DNA damage.
Fukuoka
Kazuya
K
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Arioka
Hitoshi
H
Iwamoto
Yasuo
Y
Fukumoto
Hisao
H
Kurokawa
Hirokazu
H
Ishida
Tomoyuki
T
Tomonari
Akira
A
Suzuki
Toshihiro
T
Usuda
Jitsuo
J
Kanzawa
Fumihiko
F
Kimura
Hiroshi
H
Saijo
Nagahiro
N
Nishio
Kazuto
K
D018288:Carcinoma, Small Cell / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine
D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D014747:Vinblastine; D000077235:Vinorelbine