Research Paper Volume 13, Issue 15 pp 19750—19759

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

Dual inhibition of FGFR/BCL-xL is feasible in vivo. (A) weight monitoring of SK-OV-3 cell-implanted xenograft mice treated with 25 mg/kg/d of A-1331852, 100-mg/kg of BLU9931, Cisplatin equivalent of 75 mg/m2 of dose in humans; (B) tumor growth of SK-OV-3 cell-implanted xenograft mice treated with A-1331852 (A) and BLU9931 (B) or vehicle control with representative tumor image at endpoint, discontinued curve in control group indicating individuals reaching endpoint of tumor size; (C) Kaplan-Meier survival curve of control and treatment group compared by Log-rank test; (D) representative immunohistochemical staining of BCL-xL in extracted tumors; (E) schematic cartoon showing association between FGFR4/NCAM and BCL2L1 with drug sensitivity profile in the setting of current study. (N = 10 in all assays; Scale bar = 1cm; *P

Figure 4. Dual inhibition of FGFR/BCL-xL is feasible in vivo. (A) weight monitoring of SK-OV-3 cell-implanted xenograft mice treated with 25 mg/kg/d of A-1331852, 100-mg/kg of BLU9931, Cisplatin equivalent of 75 mg/m2 of dose in humans; (B) tumor growth of SK-OV-3 cell-implanted xenograft mice treated with A-1331852 (A) and BLU9931 (B) or vehicle control with representative tumor image at endpoint, discontinued curve in control group indicating individuals reaching endpoint of tumor size; (C) Kaplan-Meier survival curve of control and treatment group compared by Log-rank test; (D) representative immunohistochemical staining of BCL-xL in extracted tumors; (E) schematic cartoon showing association between FGFR4/NCAM and BCL2L1 with drug sensitivity profile in the setting of current study. (N = 10 in all assays; Scale bar = 1cm; *P < .05; **P < .01; ***P < .001; ****P < .0001).