TY - JOUR T1 - Inhibition of Heat-shock Protein 27 Expression Eliminates Drug Resistance of Osteosarcoma to Zoledronic Acid JF - Anticancer Research JO - Anticancer Res SP - 3565 LP - 3571 VL - 30 IS - 9 AU - TAKESHI MORII AU - KOUKI OHTSUKA AU - HIROAKI OHNISHI AU - KAZUO MOCHIZUKI AU - KAZUHIKO SATOMI Y1 - 2010/09/01 UR - http://ar.iiarjournals.org/content/30/9/3565.abstract N2 - Background: Although zoledronic acid (ZOL) has been reported to show anti-tumour effects on various malignant tumours, few studies have reported the molecular mechanisms of resistance to ZOL. Materials and Methods: A drug-resistant cell line was developed by repeatedly treating human osteosarcoma cell line HOS with ZOL. Expression status of drug resistance-related molecules including ATP-binding cassette (ABC) and heat-shock protein 27 (HSP27) was confirmed in order to analyse molecular mechanisms of the drug resistance. Results: Repeated treatment with ZOL induced drug resistance with down-regulation of apoptosis in the resistant cell line. Although ABC expression was down-regulated, up-regulation of HSP27 in the resistant cell line was confirmed. The resistance was overcome by HSP27 silencing. Conclusion: Resistance to ZOL in osteosarcoma cells may be induced by a molecular mechanism different from conventional efflux pump-based resistance. Up-regulation of HSP27 expression may play a role in the development of ZOL resistance in HOS cells. ER -