Dinaciclib

Different co-treatments or pre-treatment strategies were followed for each combined therapy. For liposomal doxorubicin and olaparib treatment, the cells were pre-treated for 6 h with 100 nM Dox-NP (Avanti^®, Alabaster, AL, USA), followed by treatment for 60 h with 1 μM olaparib. For temozolomide (TMZ) (Sigma Aldrich, Taufkirchen, Germany) and olaparib co-treatment, the cells were pre-treated for 48 h with 50 μM temozolomide before co-treatment with 1 μM olaparib for 24 h. Single treatments with [¹²⁵I]-PARPi-01 (~1 MBq/10⁶ cells), olaparib (1 μM), dinaciclib (5 μM; Sigma), and talazoparib (10 nM; Axon Medchem, Groningen, Netherlands.) were done for 72 h, dinaciclib (5 μM), and 1 μM olaparib co-treatment was done for 72 h. For Dox-NP and [¹²⁵I]-PARPi-01 combination, the cells were pre-treated with 100 nM Dox-NP 6 h prior to incubation with [¹²⁵I]-PARPi-01 (~1MBq/10⁶ cells) for 72 h. Untreated cells were incubated in growth medium supplemented with DMSO (≤0.2%) for 72 h.

Dinaciclib was obtained from Selleck Chemicals and was dissolved in DMSO (Sigma) to a concentration of 10 mM and stored at -80°C until further use in vitro experiments. For the in vivo studies, Dinaciclib was diluted in 20% (w/v) of 2-hydroxypropyl-β-cyclodextrin (Sigma) and stored at -30°C until use.

The small‐molecule compounds were purchased from Selleck (SNS‐032, Dinaciclib, GSK126, EPZ‐6438 (Tazemetostat), Bobcat339) and Sigma–Aldrich (5‐aza‐2′‐deoxycytidine). For cell treatment, cells were seeded in 6 well plate at 30%–50% confluency overnight and treated with SNS‐032 (100 nM), Dinaciclib (25 nM), GSK126 (5 µM), EPZ‐6438 (10 µM) and 5‐Aza‐dC (10 µM) for 3 days, with Bobcat339 (40 and 80 µM) for 4 days. Control cells were treated with the corresponding amount of vehicle (DMSO).

Dinaciclib were purchased from (ChemieTek and Sigma). Dinaciclib were prepared in stock solution of 10mM in Dimethyl sulphoxide (Sigma) for in-vitro experiments.