title: Lung cancer cell line sensitivity to Zoledronic acid is BAX-dependent.
abstract: BACKGROUND
  Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear.
  
  
  METHODS
  Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance.
  
  
  RESULTS
  Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance.
  
  
  CONCLUSIONS
  Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.
authors: Department of Orthopaedic Surgery, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan. t-morii@gb3.so-net.ne.jp.
authors: Takayuki
authors: T
authors: Aoyagi
authors: Takeshi
authors: T
authors: Morii
authors: Kouki
authors: K
authors: Ohtsuka
authors: Hiroaki
authors: H
authors: Ohnishi
authors: Takashi
authors: T
authors: Tajima
authors: Akira
authors: A
authors: Yoshiyama
authors: Kazuo
authors: K
authors: Mochizuki
authors: Kazuhiko
authors: K
authors: Satomi
authors: Shoichi
authors: S
authors: Ichimura
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D000077211:Zoledronic Acid; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D051028:bcl-2-Associated X Protein; D000077211:Zoledronic Acid
keywords: BAX; Lung cancer; drug resistance; zoledronic acid