title: Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines.
abstract: Small cell lung cancer (SCLC) is one of the most aggressive types of cancers because of its early development of regional and distant metastases. Novel and more effective therapeutic strategies for the treatment of this disease are necessary. Bisphosphonates (BP), originally developed to treat bone disease, have recently been identified as attractive cancer theraptic agents. In this study, we investigated the anti-proliferative effects of zoledronic acid (ZOL) as a single agent and in combination with other agents. ZOL inhibited both farnesylation and geranylgeranylation of RAS related proteins, induced apoptosis and inhibited the growth of eight out of twelve SCLC cell lines examined the in vitro. ZOL also significantly inhibited SCLC tumor growth and SBC-3 cells transplanted subcutaneously into nude mice. Its suppressive effect have not been completed, the addition effect of ZOL with other agents was examined. ZOL augmented the effects of paclitaxel, etoposide, cisplatinum and irinotecan synergistically, and imatinib mesylate additively. These findings indicate that ZOL and combined use of these agents may be promising therapeutic strategies for SCLC.
authors.affiliation: Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Segawa
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sato
authors.forename: Masaki
authors.initials: M
authors.lastname: Nogawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wada
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid