Fig. 2: BTSA1.2 and Navitoclax synergize to inhibit cell viability and induce apoptosis in various tumor cell lines.
From: Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer
a Schematic of Navitoclax and BTSA1.2 combination screening in a diverse cancer cell lines panel (n = 46). b Bar graph plot of the cell viability IC50 (μM) fold change of cancer cells treated for 72 hrs with Navitoclax in combination with a constant sensitizing concentration of BTSA1.2 (loss of cell viability 0–20%). Red bar graphs correspond to IC50 fold change > 5x; green bar graphs correspond to IC50 fold change 2-4x; and gray bar graphs correspond to IC50 fold change <2x. c Mutation status of TP53 and RAS in cancer cell lines classified as sensitive or resistant to the combination. d Dose-response curves of Navitoclax in the presence of various doses of BTSA1.2 in a panel of cancer cell lines resistant to single agents (Leukemia = U937, Colon=SW480, Pancreatic=BxPC-3, NSCLC = Calu-6). Data are mean ± SD of three technical replicates from n = 3 independent experiments. e Bliss synergy score heat map from combinatorial treatment of BTSA1.2 and Navitoclax in different cancer tissue types in b. Data represent mean from n = 3 independent experiments. f Caspase 3/7 activity assay in diverse cancer cell lines treated with BTSA1.2 and Navitoclax alone or in combination measured at 8 hrs. Data are mean ± SD of three technical replicates from n = 3 independent experiments. Statistics were obtained using two-way ANOVA: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. g Cell viability at 24hrs in WT and CRISPR/Cas9 BAX KO Calu-6 cell lines treated with Navitoclax alone in the presence of a fixed sensitizing concentration of BTSA1.2 (loss of viability <10%). Comparison of BAX and BAK protein expression levels in indicated cell lines. Data are mean ± SD of three technical replicates from n = 3 independent experiments. h Caspase 3/7 activity in WT and CRISPR/Cas9 BAX KO Calu-6 cell lines after 8 hrs treatment with Navitoclax alone and in combination with a fixed sensitizing concentration of BTSA1.2 (loss of viability <10%). Data are mean ± SD of three technical replicates from n = 3 independent experiments. Statistics were obtained using two-way ANOVA: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.
