@article {MORII3565, author = {TAKESHI MORII and KOUKI OHTSUKA and HIROAKI OHNISHI and KAZUO MOCHIZUKI and KAZUHIKO SATOMI}, title = {Inhibition of Heat-shock Protein 27 Expression Eliminates Drug Resistance of Osteosarcoma to Zoledronic Acid}, volume = {30}, number = {9}, pages = {3565--3571}, year = {2010}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/30/9/3565}, eprint = {https://ar.iiarjournals.org/content/30/9/3565.full.pdf}, journal = {Anticancer Research} }