KPT-330+CS inhibits proteins in key cellular pathways. Jeko-1 cells were treated with KPT-330 (0.5 μM), CS (3m M) as single-agent treatment and in combination for 24 hours, respectively. Subsequently, cellular proteins were cataloged through mass spectroscopy. (A-E) Volcano plots showing protein changes associated with each treatment condition; (A) KPT-330+CS vs control; (B) KPT-330 vs control; (C) CS vs control; (D) CS vs KPT-330; (E) KPT-330+CS vs KPT-330. Significantly differentially expressed proteins (absolute log₂ fold change ≥2 and false discovery rate [FDR] ≤0.05) are highlighted in red. Key proteins in cell-cycle, nucleotide synthesis, and DNA-damage repair pathways are tagged where detected. (F-H) Immunoblot images validating the findings of proteomic studies following JeKo-1 cells treated with respective drug conditions. (I) Heat map showing significantly affected pathways by KPT-330+CS. An ANOVA test was used to detect the differentially expressed protein groups and cellular pathways between pairs of experimental groups. (J) Heat map showing the downregulation of selected proteins involved in DNA-damage repair, cell-cycle progression, DNA synthesis, and nuclear molecular export. Each condition was performed in biological triplicates of the JeKo-1 cell line. Differential expression P values were FDR-corrected using Benjamini-Hochberg procedure. A total of 5 group comparisons were performed: KPT-330 vs control, CS vs control, KPT-330+CS vs control, KPT-330+CS vs KPT-330, and CS vs KPT-330. For each comparison, protein groups with an FDR ≤0.05 and an absolute log₂ (fold change) ≥2.0 were considered as significantly differentially expressed.