Figure 1.

Crizotinib causes cardiac dysfunction, myocardial injury and remodeling in mice. C57BL/6J mice (n = 5) were treated with vehicle or 100 mg/kg crizotinib for 6 weeks. (A, B) the cardiac function of C57BL/6J mice. (C) heart weight to tibia length ratio (HW: TL). (D) Representative images of cardiac sections stained by WGA. Scale bar: 20 μm. Right: quantification of cardiomyocyte cross-sectional area based on WGA staining. (E) cardiac remodeling gene expression relative to Actb. n = 4. (F) Representative images of cardiac sections stained by Sirius red or Masson. Scale bar: 50 μm. (G) MCMs (left) or CCC-HEH-2 cells (right) were treated with crizotinib for 72 h, respectively, and the survival fraction was detected via SRB assay. n = 3. (H) serum from the mice was analyzed for CKMB (left) and LDH (right) levels. n = 5. (I) H&E staining. Scale bar: 2 μm. The yellow arrow indicated typical pathological changes. Scale bar: 50 μm. (J) MCMs were treated with crizotinib. GAPDH was used as the loading control. n = 3. (K) MCMs were stained with DAPI after crizotinib (1 μM) treatment for 8 h. Yellow arrows indicate significant changes of the nucleus. Scale bar: 25 μm. Data were presented as mean ± SD. The P value was calculated by unpaired Student’s t test (B to E and H) and one-way ANOVA with Dunnett’s multiple comparisons tests (G and J). ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05; ns, no significance. CTRL: Control; Crizo: crizotinib.