Fig. 2: Sotorasib induces apoptosis and mitochondrial dysfunction in cardiomyocytes.
From: Sotorasib-impaired degradation of NEU1 contributes to cardiac injury by inhibiting AKT signaling
A CC-HEH-2 cells were treated with 0, 7.5, 15, 30, 60 μM sotorasib for 48 h; H9c2 cells were treated with 0, 7.5, 15, 30, 60 μM sotorasib for 48 h (n = 3). Representative pictures. Scale bars: 50 μm. B CCC-HEH-2 cells were treated with 0, 3.75, 7.5, 15, 30, 60 μM sotorasib for 48 h; H9c2 cells were treated with 0, 3.75, 7.5, 15, 30, 60 μM sotorasib for 48 h. Survival fraction detection by SRB colorimetric assay (n = 3). C CCC-HEH-2 cells were exposed to different concentrations of 0, 10, 15, or 20 μM sotorasib for 48 h. H9c2 cells were exposed to different concentrations of 0, 30, 45, or 60 μM sotorasib for 48 h. Expression levels of c-PARP protein in CCC-HEH-2 and H9c2 cells. D Male C57BL/6J mice were treated with 0.5% CMC-Na or sotorasib (300 mg/kg/d or 600 mg/kg/d) by gavage for 28 days (n = 6). Representative image of IHC staining of cardiomyocytes c-CAPSP3 (n = 3). Scale bars: 100 μm. E CCC-HEH-2 were treated with 20 μM sotorasib for 0, 12, 24, 36, and 48 h and exposed to different concentrations of 0, 10, 15, or 20 μM sotorasib for 48 h. The apoptosis rate of CCC-HEH-2 cells (n = 3). F 20 μM sotorasib and/or 20 μM Z-VAD-FMK treated CCC-HEH-2 for 48 h. Expression level of c-PARP in CCC-HEH-2 cells (n = 3). G CCC-HEH-2 were exposed to different concentrations of 0, 10, 15, or 20 μM sotorasib for 48 h. MMP changes in CCC-HEH-2 cells (n = 3). H CCC-HEH-2 and were exposed to different concentrations of 0, 10, 15, or 20 μM sotorasib for 24 h. ATP levels in CCC-HEH-2 cells (n = 3). I 20 μM sotorasib treatment of CCC-HEH-2 cells for 0, 6, 9, 12 and 24 h. ROS levels in CCC-HEH-2 cells (n = 3). J Male C57BL/6J mice were treated with 0.5% CMC-Na or sotorasib (300 mg/kg/d or 600 mg/kg/d) by gavage for 28 days (n = 6). Transmission electron microscopy representative images. scale bars: 2 μm. Data expressed as mean ± SD, ***, p < 0.0001, **, p < 0.01, *, p < 0.05 (vs. Vehicle), #, p < 0.05 (vs. sotorasib), &, p < 0.05 (vs. Z-VAD-FMK), ns, no significance.
