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.