Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity. In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHaCDV and HeLaCDV) and one HPV(-) (HaCaTCDV) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug-resistance (MRP2, P-gp, BCRP) was also investigated. Alterations of CDV metabolism in SiHaCDV and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHaCDV and HeLaCDV, respectively. Altered transporters expression in SiHaCDV and/or HeLaCDV, but not in HaCaTCDV, was also noted. Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process.

• MeSH
• ABC transportéry biosyntéza   MeSH
• chemorezistence genetika   MeSH
• cytidintrifosfát biosyntéza   MeSH
• cytosin analogy a deriváty   farmakologie   MeSH
• fosforylace MeSH
• HeLa buňky MeSH
• infekce papilomavirem farmakoterapie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• nádorové buněčné linie MeSH
• nádory děložního čípku farmakoterapie   patologie   virologie   MeSH
• nukleosidmonofosfátkinasa biosyntéza   metabolismus   MeSH
• organofosfonáty farmakologie   MeSH
• Papillomaviridae MeSH
• SLC transportéry biosyntéza   MeSH
• uridintrifosfát biosyntéza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH