Concomitant resistance to paclitaxel in an ovarian cancer cell variant selected with carboplatin (CROSBI ID 675450)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Kralj, Juran ; Duran, George E. ; Stupin Polančec, Darija ; Bačić, Niko ; Sikic, Branimir I. ; Brozovic, Anamaria
engleski
Concomitant resistance to paclitaxel in an ovarian cancer cell variant selected with carboplatin
Most epithelial ovarian cancer patients are diagnosed with advanced-stage disease due to the late appearance of symptoms and lack of early diagnostic methods/markers. The major problem for successful therapy is the development of tumour drug resistance during carcinogenesis (20-30%) and upon exposure to chemotherapy. The ovarian cancer cell line OVCAR-3/CBP was established by treatment of the ovarian adenocarcinoma cell line OVCAR-3 with long-term, stepwise selection in carboplatin (CBP) up to 25 μM. The variant is ~1.5-2-fold resistant to CBP, with cross-resistance to paclitaxel (TAX, ~4-fold), and presents with a mesenchymal-like phenotype. The increased expression of NHE-1, ATP7-B and decreased expression of ABCC2 and CTR-1 implied decreased total cell platination as a possible mode of CBP resistance, which was confirmed by flame atomic absorption spectrometry. Despite the increased level of ABCB1 transcripts, OVCAR-3/CBP did not efflux [3H]-docetaxel differently compared to parental cells, and the P-glycoprotein inhibitor PSC-833 did not alter these drug accumulation profiles. This indicates that the TAX resistance in OVCAR-3/CBP is non-MDR, but is associated with elevated TUBB3 (class III beta-tubulin) content along with total α- and β-tubulin relative to parental OVCAR-3 cells. In summary, drug selection with carboplatin in an ovarian cancer cell line resulted in non-MDR cross-resistance to paclitaxel. Experiments investigating the functional significance of altered tubulin content and microtubule dynamicity in response to drug exposure in OVCAR-3/CBP are on-going.
drug resistance ; ovarian cancer ; tubulin ; molecular mechanisms ; therapy
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Podaci o prilogu
51-51.
2018.
objavljeno
Podaci o matičnoj publikaciji
4th Congress of Croatian Geneticists with international participation : book of abstracts
Šarčević, Hrvoje ; Ugarković, Đurđica ; Vujaklija, Dušica ; Svetec, Ivan Krešimir ; Svetec Miklenić, Marina.
Zagreb: Hrvatsko genetičko društvo
978-953-57128-1-7
Podaci o skupu
4th Congress of Croatian Geneticists with international participation
poster
26.09.2018-29.09.2018
Krk, Hrvatska