Naslov
Concomitant resistance to paclitaxel in an ovarian cancer cell variant selected with carboplatin

Autori
Kralj, Juran ; Duran, George E. ; Stupin Polančec, Darija ; Bačić, Niko ; Sikic, Branimir I. ; Brozovic, Anamaria

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
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, 2018, 51-51

ISBN
978-953-57128-1-7

Skup
4th Congress of Croatian Geneticists with international participation

Mjesto i datum
Krk, Hrvatska, 26.09.2018. - 29.09.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
drug resistance ; ovarian cancer ; tubulin ; molecular mechanisms ; therapy

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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