Fig. 3: NHEJ and HR pathway inhibition selectively sensitizes PDAC cells to CIRT. | npj Precision Oncology

Fig. 3: NHEJ and HR pathway inhibition selectively sensitizes PDAC cells to CIRT.

From: Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer

Fig. 3

Clonogenic survival assays were performed to compare the radiation sensitivities of PANC03.27 (A) and MIA-PaCa-2 (D) cells in the presence of DNA damage response inhibitors. Cells were pretreated with DMSO (Control), 3 μM NU7441 (DNA-PKi), 20 μM B02 (RAD51i), or 100 nM AZD6738 (ATRi) and then irradiated at the indicated doses of γ-rays (solid) or carbon ions (dashed) and plated for analysis of survival and colony-forming ability. B, E Sensitization enhancement ratio (SER) was calculated using the mean inactivation dose (MID) for each clonogenic survival (γ-rays or carbon ions) and calculating the ratio of the control (DMSO) vs each inhibitor individually. Variance (VAR), standard deviation (StDEV), and p values as generated by a student’s t-test are also shown. Immunostaining of γH2AX foci in PANC03.27 (C) and MIA PaCA-2 (F) cells after pretreatment with DMSO (control), 3 μM NU7441 (DNA-PKi), 20 μM B02 (RAD51i), or 100 nM AZD6738 (ATRi), and then exposed to 1 Gy of γ-rays (solid) or carbon ions (crosshatch). Cells were fixed at 0.5 h, 8 h, and 24 h after IR and immunostained for γH2AX foci. γH2AX foci were counted for each cell and averaged. Student’s t-test (two-sided) was performed to assess statistical significance (****p < 0.0001).

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