Lung cancer cell line sensitivity to Zoledronic acid is BAX-dependent.
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.


MATERIALS AND 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.


CONCLUSION
Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.
['Aoyagi|Takayuki|T|', 'Morii|Takeshi|T|', 'Ohtsuka|Kouki|K|', 'Ohnishi|Hiroaki|H|', 'Tajima|Takashi|T|', 'Yoshiyama|Akira|A|', 'Mochizuki|Kazuo|K|', 'Satomi|Kazuhiko|K|', 'Ichimura|Shoichi|S|']
D017209:Apoptosis D002289:Carcinoma, Non-Small-Cell Lung D045744:Cell Line, Tumor D049109:Cell Proliferation D004164:Diphosphonates D004797:Enzyme-Linked Immunosorbent Assay D005434:Flow Cytometry D006801:Humans D007093:Imidazoles D008175:Lung Neoplasms D034622:RNA Interference D000077211:Zoledronic Acid D051028:bcl-2-Associated X Protein
Lung cancer zoledronic acid BAX drug resistance