Contribution of different molecular mechanisms to cisplatin resistance in human cervical carcinoma cell lines (CROSBI ID 483667)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa
Podaci o odgovornosti
Brozović, Anamaria ; Osmak, Maja ; Fritz, G. ; Kaina, B.
engleski
Contribution of different molecular mechanisms to cisplatin resistance in human cervical carcinoma cell lines
Acquired drug resistance is a major problem in tumor chemotherapy. Cisplatin (cDDP) is widely used as an anticancer drug. In this study we investigated the mechanisms involved in resistance of human tumor cells to cDDP. Two human cervical carcinoma cell lines were used in those experiments: parental (HeLa) cells and two cDDP-resistant cell lines (HeLa CA and HeLa CK). Mismatch repair ( MMR) and nucleotide excision repair ( NER) were not involved in resistance to cDDP in human cervical carcinoma cells. Replication inhibition, the formation of DNA single-strand and double-strand breaks and the formation of interstrand DNA cross-links were similar in parental and cDDP-resistant cell lines. The expression of canalicular multispecific organic anion transporter protein was similar in all three examined cell lines. However, cDDP induced a higher frequency of apoptotic cell death in parental HeLa than in HeLa CA and HeLa CK cells. Also, activation of c-Jun-terminal protein kinase ( JNK) and p3 8 kinase, binding of AP-1 transcription factor and c-Jun protein expression were reduced in the resistant cell lines. Furthermore, after the treatment with cDDP HeLa cells were blocked in G2 phase wheres HeLa CK cells progressed normally through the cell cycle. Based on this data we suggest that increased activation of the MAP kinase pathway contributes to the cisplatin sensitive phenotype by provoking programmed cell death.
cisplatin
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o prilogu
2002.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
DNA repair 2002 7. Tagung des DNA-Reparatur-Netzwerks
predavanje
17.09.2002-20.09.2002
Karlsruhe, Njemačka