Fig. 5

Inhibition of MAPK pathway prevents DNA damage and reverses nuclear abnormality in sotorasib-resistant cells. A The MIA-SR and H23-SR was cultured with or without 5 μM sotorasib, 200 nM cobimetinib, or both. γ-H2AX (red) was detected through immunofluorescence. −: < 5 foci/cell, +: > 5 foci/cell, and + + : pan-nuclear expression. B The MIA-SR and H23-SR cells were cultured with or without 5 μM sotorasib, 200 nM cobimetinib, or both. The degree of DNA strand breaks was measured through comet assay. C, D Representative images of immunofluorescence staining and quantification of nucleoplasmic bridges (C) and micronuclei (D) in the MIA-SR cells cultured with or without sotorasib, 200 nM cobimetinib, or both. The yellow arrows denote the locations of nucleoplasmic bridges (C) or micronuclei (D). A minimum of 200 nuclei per condition were analyzed (A, C, D). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001