TY  - JOUR
A1  - Michaelis, Martin
A1  - Voges, Yvonne
A1  - Rothweiler, Florian
A1  - Weipert, Fabian
A1  - Zia-Ahmad, Amara
A1  - Cinatl, Jaroslav
A1  - Deimling, Andreas von
A1  - Westermann, Frank
A1  - Rödel, Franz
A1  - Wass, Mark N.
A1  - Cinatl, Jindrich
T1  - Testing of the survivin suppressant YM155 in a large panel of drug-resistant neuroblastoma cell lines
T2  - Cancers
N2  - The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
KW  - YM155
KW  - survivin
KW  - neuroblastoma
KW  - drug resistance
KW  - ABCB1
KW  - ABCC1
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54329
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-543298
SN  - 2072-6694
VL  - 12
IS  - 577
PB  - MDPI
CY  - Basel
ER  -