Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00461337" target="_blank" >RIV/61388963:_____/16:00461337 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.18632/oncotarget.7006" target="_blank" >http://dx.doi.org/10.18632/oncotarget.7006</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/oncotarget.7006" target="_blank" >10.18632/oncotarget.7006</a>

Result language
angličtina
Original language name
Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1
Original language description
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(+) (SiHa(CDV) and HeLaCDV) and one HPV(-) (HaCaT(CDV)) 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 SiHa(CDV) 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 SiHa(CDV) and HeLaCDV, respectively. Altered transporters expression in SiHa(CDV) 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.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CC - Organic chemistry
OECD FORD branch
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Project
<a href="/en/project/GA14-00522S" target="_blank" >GA14-00522S: Syntheses of new prodrug forms of biologically active nucleotide analogues</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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