Skip to main content
. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Gastroenterology. 2021 Mar 19;161(1):196–210. doi: 10.1053/j.gastro.2021.03.022

Figure 2.

Figure 2.

Selective XPO1 inhibition drives DNA damage-dependent lethality in CRC (A) XPO1 expression level across CRC models (black, cell lines and PDX-derived primary cultures) and colon epithelial cells (light blue). (B) Knockdown efficiency of XPO1 using 2 independent shRNAs in B1011 PDX-derived cell line compared to 2 shNT (Non-targeting) controls. (C) Colony formation assay in C0999, B1003 and B1011 cells expressing shNT or XPO1-targeting shRNA. (D) Sensitivity to KPT-330 across a panel of CRC models (cell lines and PDX-derived primary cultures) and colon epithelial cells (light blue) based on ATP viability assay (96h). (E) Expression of indicated proteins in CRC (black) or normal colon epithelial (light blue) cells treated with KPT-330 at indicated doses for 24h. (F) Nuclear fraction of protein expression in B1011 PDX-derived cells treated with KPT-330 at indicated dose for 24h. 5-FU serves as positive control. (G) Immunofluorescence staining of phospho-H2A.X and DAPI in B1011 PDX-derived primary cells treated with DMSO or KPT-330 at indicated doses for 24h. (H) FACS analysis for cell-cycle (BrdU incorporation) and DNA damage accumulation (phospho-H2A.X). β-actin and Histone H3 serve as loading controls in Western analyses. Representative image from 3 independent experiments is shown. All data are mean ± S.D. of biological replicates (n=3 each). All the experiments were repeated 3 times.