Naslov
The interplay between tubulin β isotypes and drug response in ovarian cancer cell lines resistant to carboplatin

Autori
Pernar Kovač, Margareta ; Tadić, Vanja ; Kralj, Juran ; Duran, George E. ; Stefanelli, Alessia ; Stupin Polančec, Darija ; Dabelić, Sanja ; Bačić, Niko ; Tomicic, Maja ; Heffeter, Petra ; Sikic, Branimir I. ; Brozovic, Anamaria

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

Izvornik
International Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22 "From Science to Knowledge", Book of Abstracts / Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana - Zagreb : Hrvatsko Društvo za Biotehnologiju, 2022, 116-116

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology: From Science to Knowledge (HDBMB22)

Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
carboplatin resistance, ovarian cancer, paclitaxel, tubulin, cellular trafficking

Sažetak
Ovarian cancer (OC) is the seventh most common cancer type in women worldwide. Unfortunately, lack of early detection methods leads to diagnosis of already advanced disease tied with highest fatality-tocase ratio among gynecological malignancies. Conventional therapy for OC consists of cytoreductive surgery followed by chemotherapy with carboplatin (CBP) and paclitaxel (TAX). However, 80% of late-diagnosed patients experience relapse due to the acquired resistance and frequently develop metastases. It is important to emphasize that resistance mechanisms to CBP and TAX involve mostly different pathways and up till now these two processes have been studied separately. Here, we explored CBP-induced TAX cross-resistance with aim to identify possible linkers of CBP and TAX drug response and potential use of those molecules as predictive biomarkers. For this purpose, we used two different mesenchymal-like OC cell models developed by stepwise CBP treatment of parental MES-OV and SK- OV-3 cell lines, CBP-resistant and TAX cross- resistant MES-OV CBP cell line and CBP-resistant but TAX sensitive SK-OV-3 CBP cell line. Interestingly, both cell lines showed elevated levels of class III β-tubulin (TUBB3) however, transient silencing of TUBB3 only impacted MES-OV CBP response to CBP while SK-OV-3 CBP did not show any sensitization. Additionally, reduced levels of TUBB3 in MES-OV CBP cell line disturbed the trafficking of RAD50, MRN complex protein involved in DNA damage repair, and increased whole-cell platination levels. Both of these processes implied involvement of TUBB3 silencing in CBP sensitization of MES-OV CBP cells. The difference between these two cell lines was the compensation of TUBB3 silencing with other β-tubulin isotypes noticed in SK-OV-3 CBP, but absent in MES-OV CBP cell line. Based on this we proposed that TUBB3, despite upregulation in both cases, can be used as a predictive marker for treatment efficacy only when β-tubulin isotype compensation is lacking.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA