Figure 5 from Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7–Expressing CRPC Models
<p>Dual targeting of Bcl-xL and Mcl-1 leads to synergistic decreases in cell viability in 3D LNCaP95 spheroids and the LuCaP 167CR organoid model. Dual treatment of navitoclax and A-1331852 with S63845 in 3D prostate cancer models. <b>A,</b> Representative images for each treatment condition before treatment and 24, 48, and 72 hours after treatment. <b>B</b> and <b>C,</b> Viability of spheroids measured by 3D CellTiter-Glo after 72 hours of treatment. Plots show mean ± SD. ****, <i>P</i> < 0.0001. LuCaP-167CR organoids were treated with the combination of A-1331852 and S63845 (<b>D–F</b>) or navitoclax and S63845 (<b>G–I</b>). Drug curves (<b>D</b> and <b>G</b>) show mean ± SD. Dose–response matrices (<b>E</b> and <b>H</b>) and Bliss synergy plots (<b>F</b> and <b>I</b>) were generated using the Synergyfinder+ R package to evaluate synergy. All spheroid experiments were completed in triplicate. Organoid experiments had six technical replicates with three biological replicates.</p>
Authors
- Kelli M. Wilson (ORCID: https://orcid.org/0000-0003-2636-2766)
- Erin Beck
- Andres F. Leon (ORCID: https://orcid.org/0009-0003-3187-6582)
- Craig J. Thomas (ORCID: https://orcid.org/0000-0001-9386-9001)
- Kinjal Bhadresha
- Xiaohu Zhang (ORCID: https://orcid.org/0000-0002-5872-4656)
- Keith Thomas Schmidt (ORCID: https://orcid.org/0009-0008-0285-0216)
- Jessica D. Kindrick (ORCID: https://orcid.org/0000-0003-1519-9721)
- Adam G. Sowalsky (ORCID: https://orcid.org/0000-0003-2760-1853)
- Carleen Klumpp‐Thomas (ORCID: https://orcid.org/0000-0002-6646-6132)
- Michele Ceribelli (ORCID: https://orcid.org/0000-0001-9857-9521)
- Erica L. Beatson (ORCID: https://orcid.org/0000-0003-4517-906X)
- Crystal McKnight (ORCID: https://orcid.org/0009-0007-6554-5772)
- Giulia C. Napoli (ORCID: https://orcid.org/0009-0006-7354-8693)
- Douglas K. Price (ORCID: https://orcid.org/0000-0002-7051-7510)
- William D. Figg (ORCID: https://orcid.org/0000-0003-2428-5613)
- Emily N. Risdon (ORCID: https://orcid.org/0000-0002-5888-8634)
- JuanJuan Yin (ORCID: https://orcid.org/0000-0001-6739-5463)
- Cindy H. Chau (ORCID: https://orcid.org/0000-0002-6928-3833)
- Benjamin C. Brim (ORCID: https://orcid.org/0000-0002-6713-3292)
Publication Details
- Published
- 2025-08-21
- DOI
- https://doi.org/10.1158/2767-9764.29957555
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00