Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

Figures

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  Figure 1. Resveratrol (RES) and 5-fluorouracil (5-Fu) synergistically induced MFC cell growth arrest and cell death. A, Chemical structure of resveratrol. B, The impact of various treatments, including 5-Fu, RES, and 5-Fu + RES, on the cell viability of MFC gastric cancer cells was evaluated after a 24-h exposure period. C, Apoptotic percentage of each group. Graphs were partitioned into four quadrants representing late apoptotic cells, dead cells, live cells, and early apoptotic cells. The apoptotic percentage of the Control group was 10.9±0.5%, 5-Fu group was 17.9±3%, RES group was 14.2±3.5%, and 5-Fu + RES group was 25.8±6.5%. D, Histogram depicting the percentage of apoptotic MFC cells. E, Transwell assays were used to detect invasive and migratory abilities of MFC cells in the absence or presence of 5-Fu and RES, alone or in combination for 24 h (scale bar 50 μm). F and G, Histogram of the number of invasive cells and migrated cells. Data are reported as means±SE. *P<0.05, **P<0.01, ***P<0.001 vs Control group; #P<0.05 vs 5-Fu group; ##P<0.01 vs RES (n=4, ANOVA).

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  Figure 2. Resveratrol (RES) synergistically with 5-fluorouracil (5-Fu) induced apoptosis. A, Representative photograph of tumors from each group. B, Statistical analysis of tumor weight. C, Statistical analysis of tumor volume (n=8). Effect of RES and 5-Fu on Bcl-2 protein expression (D), Bax protein expression (E), p53 protein expression (F), and LC3 protein expression (G) in tumor tissues. Data are reported as means±SE. *P<0.05, **P<0.01, ***P<0.001 vs Control (Model) group; #P<0.05 vs 5-Fu group (n=3, ANOVA).

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  Figure 3. Resveratrol (RES) enhanced cardioprotection against 5-fluorouracil (5-Fu)-induced myocardial injury. A, Representative cardiac ultrasound image of each group. B, Statistical analysis of cardiac ejection fraction (EF) in each group. C, Statistical analysis of the short-axis shortening (FS) rate of the left ventricle in each group. D, Representative images of HE staining of myocardial tissue (scale bar 100 μm). E, Malondialdehyde (MDA) levels, F, total glutathione (GSSG+GSH) levels, G, reduced GSH levels, H, superoxide dismutase (SOD) levels, and I, catalase (CAT) levels in mouse heart tissues of each group. Data are reported as means±SE. *P<0.05, ***P<0.01 vs Control (Model) group; #P<0.05, ##P<0.01, ###P<0.001 vs 5-Fu group (n=3, ANOVA).

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  Figure 4. Resveratrol (RES) alleviated 5-fluorouracil (5-Fu)-induced oxidative stress in cardiomyocytes. A, Green fluorescence intensity represents the level of reactive oxygen species (ROS) in myocardial cells (scale bar 100 μm). B, Statistical graph of fluorescence intensity of cardiomyocytes in each group. C and D, Statistical graphs of changes in malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels in cardiomyocytes of each group. Data are reported as means±SE. *P<0.05, **P<0.01 vs Control group; #P<0.05 vs 5-Fu group (n=3, ANOVA).

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  Figure 5. Resveratrol (RES) inhibited apoptosis and autophagy in cardiomyocytes promoted by 5-fluorouracil (5-Fu). A, Cell viability of MFC gastric cancer cells after 24 h treatment in control, 5-Fu, RES, and 5-Fu + RES groups. B, Apoptotic percentage of primary cardiomyocyte. The apoptotic percentage of 5-Fu group was 32.1±3.9%, RES group was 25.2±2.4%, and 5-Fu+RES group was 27.8±3.5%. C, Histogram of the relative apoptotic rate of MFC cells. D-I, Expression of p53 protein, Bcl-2 protein, Bax protein, and LC3-I and LC3-II proteins in primary cardiomyocytes. J, Protein ratio of LC3-I/β-actin and LC3-II/β-actin. Data are reported as means±SE. **P<0.01, ***P<0.001 vs Control group; #P<0.05 vs 5-Fu group (n=4, ANOVA).