6533b7d4fe1ef96bd12628cb

RESEARCH PRODUCT

Downregulation of RhoB GTPase confers resistance to cisplatin in human larygneal carcinoma cells

Gerhard FritzNevenka MikacMaja OsmakTamara ČImbora-zovko

subject

Cancer ResearchProgrammed cell deathGenetic enhancementRHOBmedicine.medical_treatmentDown-RegulationAntineoplastic AgentsBiologyDownregulation and upregulationCell Line TumormedicineCarcinomaHumansGene silencingrhoB GTP-Binding ProteinLaryngeal NeoplasmsCisplatinChemotherapymedicine.diseaseCell biologyOncologyDrug Resistance NeoplasmCancer researchcisplatin ; drug resistance ; Rho GTPases ; RhoBCisplatinmedicine.drug

description

Acquired resistance to cisplatin represents a major obstacle to an efficient chemotherapy. We found downregulation of RhoB expression in cisplatin-resistant tumor cell lines from different origin. In cisplatin-resistant laryngeal carcinoma subline overexpression of farnesylated or geranylgeranylated RhoB increased cisplatin-induced cell death, while silencing of RhoB expression diminished sensitivity of parental HEp-2 cells via decreased cellular accumulation of cisplatin. However, since RhoB silencing in additional tumor cell lines did not alter their sensitivity to cisplatin, we can assume that RhoB downregulation does not provide general protective role in cell response to cisplatin. Nevertheless, gene therapy involving restoration of RhoB expression might improve the efficiency of cisplatin treatment, especially in patients with laryngeal carcinoma that acquired resistance to this chemotherapeutic drug.

yearjournalcountryeditionlanguage
2009-11-20
10.1016/j.canlet.2010.02.025https://www.bib.irb.hr/445697