Journal: Genes & Diseases

Article Title: Targeting fatty acid synthase to overcome PARP inhibitor resistance and to create an artificial synthetic lethality for triple-negative breast cancer

doi: 10.1016/j.gendis.2025.101817

Figure Lengend Snippet: Combination synergy on DNA damage, NHEJ repair, and apoptosis. (A, B) Western blotting and quantification analyses of FASN, PARP1, γ-H2AX, and actin loading control in MDA-MB-231 and MDA-MB-436 cells treated with 5HLS, talazoparib, or the combination. (C, D) The fraction of maximum γ-H2AX induction derived using the Bliss-compatible scaling formula. (E) Host cell reactivation assay of NHEJ activity in MDA-MB-231 and MDA-MB-436 cells treated with 5HLS, talazoparib, or the combination. (F) Comparison between the observed and expected NHEJ activity inhibition by the combination using the Bliss independence model. (G) Caspasae3/7 activity assay of MDA-MB-231 and MDA-MB-436 cells treated with 5HLS, talazoparib, or the combination. (H) The fraction of maximum caspase 3/7 activation derived using the Bliss-compatible scaling formula. (I) Annexin V staining as an indicator of apoptosis in MDA-MB-231 and MDA-MB-436 cells following treatments with 5HLS, talazoparib, or the combination. (J) The fraction of maximum apoptosis induction derived using the Bliss-compatible scaling formula. n = 3; ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, and ∗∗∗∗ P < 0.0001.

Article Snippet: Antibodies against PARP1 (#66520) and phosphorylated histone H2AX (γH2AX) (#613402) were from Proteintech (Rosemont, Illinois, USA) and BioLegend (San Diego, California, USA), respectively.

Techniques: Western Blot, Control, Derivative Assay, Host-Cell Reactivation, Activity Assay, Comparison, Inhibition, Activation Assay, Staining

Journal: Genes & Diseases

Article Title: Targeting fatty acid synthase to overcome PARP inhibitor resistance and to create an artificial synthetic lethality for triple-negative breast cancer

doi: 10.1016/j.gendis.2025.101817

Figure Lengend Snippet: In - vivo effect of 5HLS and talazoparib combination on tumor growth. (A) Tumor volume and body weight of mice treated by vehicle (Veh), 5HLS, talazoparib (Tal), or combination (Comb) of 5HLS and talazoparib. (B, C) Gross anatomy (B) and wet weight (C) of dissected xenograft tumors at the end of the study. (D) Synergy analysis. Tumor growth inhibition (TGI) was derived using the wet weight of tumors. The expected combination inhibition (C (E) ) was calculated from that of 5HLS and talazoparib alone using the Bliss independence model (see Materials and Methods ). C (O) represents the observed combination inhibition. (E) Immunohistochemical analyses of FASN, PARP, and γH2AX. Scale bar, 50 μm. (F) Western blotting analyses of FASN, BRCA1, PARP1, cleaved PARP1 (cPARP1), γH2AX, and actin loading control in xenograft tumors from mice treated with vehicle, 5HLS, talazoparib, and the combination of 5HLS and talazoparib. Each lane represents mixed samples of five tumors in equal proportion within the treatment group. n = 5; ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001.

Article Snippet: Antibodies against PARP1 (#66520) and phosphorylated histone H2AX (γH2AX) (#613402) were from Proteintech (Rosemont, Illinois, USA) and BioLegend (San Diego, California, USA), respectively.

Techniques: In Vivo, Inhibition, Derivative Assay, Immunohistochemical staining, Western Blot, Control