ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Friday, July 22, 2016

ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells



Abstract
 
Methods:
We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays.

Conclusions:
We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients.

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