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Downregulation of RhoB GTPase confers resistance to cisplatin in human laryngeal carcinoma cells
Authors:Tamara Čimbora-Zovko  Gerhard Fritz  Nevenka Mikac  Maja Osmak
Affiliation:1. Laboratory for Genotoxic Agents, Division of Molecular Biology, Ru?er Boškovi? Institute, Bijeni?ka 54, 10000 Zagreb, Croatia;2. Institute of Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany;3. Laboratory for Physical Chemistry of Traces, Division for Marine and Environmental Research, Ru?er Boškovi? Institute, Bijeni?ka 54,10000 Zagreb, Croatia
Abstract: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.
Keywords:Cisplatin   Drug-resistance   Rho GTPases   RhoB
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