Fig. 8: CRPC cells with acquired resistance to capivasertib remain sensitive to AKT and MCL1 co-inhibition. | Nature Communications

Fig. 8: CRPC cells with acquired resistance to capivasertib remain sensitive to AKT and MCL1 co-inhibition.

From: Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer

Fig. 8

A, B Comparison of capivasertib dose-response curves (left panel), capivasertib IC50 (central panel) and basal cell growth (fold change to day 0; right panel) between Capi-R and parental LNCaP95 (A) and C4-2 (B) cells. A two-sided unpaired t-test assuming normal distribution was performed. Comparison of capivasertib dose-response curves (left panel) and capivasertib IC50 (right panel) in presence and absence of AZD5991 (1 µM, 24 h) between Capi-R and parental cells in LNCaP95 (C) and C4-2 (D). Floating bars (min to max) with line at mean are depicted. One-way ANOVA with Tukey’s post-hoc test was performed. Caspase 3/7 activity at 6 h (left panel) and cell viability at 24 h (right panel) in parental and Capi-R LNCaP95 (E) and C4-2 (F) cells treated with vehicle (DMSO), capivasertib (1 µM), AZD5991 (1 µM) and combined treatment. Two-way ANOVA with Tukey’s post-hoc test was performed. Cell viability and caspase 3/7 activity were determined using Caspase-Glo 3/7 2D assay and CellTiter-Glo 2D, respectively. Protein expression of cleaved PARP and cleaved caspase 3 (at 6 h; determined by western blot) in LNCaP95 (G) and C4-2 (H) treated with vehicle (DMSO), capivasertib (1 µM), AZD5991 (1 µM) and combined treatment (combo). Comparison of protein levels of BIM, BAD, BAK, total and p-AKTSer473 between parental and Capi-R cells in LNCaP95 (I) and C4-2 (J). Protein levels of total and p-BADSer136, total BAD, and p-AKTSer473 in response to vehicle (DMSO) and varying capivasertib concentrations (0.1 µM 0.5 µM, 1 µM, 5 µM) between parental and Capi-R cells in LNCaP95 (K) and C4-2 (L). Vinculin was used as a housekeeping protein. All the experiments were performed in three biological triplicates (apart from the western Blot shown in (H and J); n = 1) and technical singlets. The standard error of the mean is shown. Asterisks (*p  <  0.05; **p  <  0.01; ***p  <  0.001) indicate statistically significant differences between groups. Source data and exact p values are provided as a Source Data file.

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