Research Paper Volume 13, Issue 15 pp 19750—19759

Dual inhibition of FGFR4 and BCL-xL inhibits multi-resistant ovarian cancer with BCL2L1 gain

Combined inhibition is needed for BCL2L1-gained OvCa. Shown were sigmoidal curve fitting for IC50s of (A) A-1331852 and BLU-9931 in SK-OV-3 cells with or without BCL2L1-KO and (B) A-1331852 in SK-OV-3 cells treated with set dose of BLU-9931 at 5 μM; (C) Cell viability of SK-OV-3 cells treated with A-1331852 (A) at 3 μM and/or BLU-9931 (B) at 5 μM and/or cisplatin (Pt) at 1 mg/mL in the 5-day course detected by MTT; (D) colony formation assay; (E) EDU-stained proliferation assay; (F) cell cycle profiling and (G) apoptosis analysis examined by flow cytometry; Transwell-based (H) invasion and (I) migration; and (J) wound-healing assay in SK-OV-3 cells treated with A-1331852, BLU-9931 and cisplatin all at 72 h of treatment with doses shown in panel (C) (N = 5 in all assays; *P

Figure 3. Combined inhibition is needed for BCL2L1-gained OvCa. Shown were sigmoidal curve fitting for IC50s of (A) A-1331852 and BLU-9931 in SK-OV-3 cells with or without BCL2L1-KO and (B) A-1331852 in SK-OV-3 cells treated with set dose of BLU-9931 at 5 μM; (C) Cell viability of SK-OV-3 cells treated with A-1331852 (A) at 3 μM and/or BLU-9931 (B) at 5 μM and/or cisplatin (Pt) at 1 mg/mL in the 5-day course detected by MTT; (D) colony formation assay; (E) EDU-stained proliferation assay; (F) cell cycle profiling and (G) apoptosis analysis examined by flow cytometry; Transwell-based (H) invasion and (I) migration; and (J) wound-healing assay in SK-OV-3 cells treated with A-1331852, BLU-9931 and cisplatin all at 72 h of treatment with doses shown in panel (C) (N = 5 in all assays; *P < .05; **P < .01; ***P < .001; ****P < .0001).