Fig. 8: DRP1 inhibitor Mdivi-1 reverses the proliferation and migration of AN3 CA cells induced by FBXO7 knockout.

A Western blotting of WCLs of AN3 CA cells with FBXO7 knockout or parental, and treated with DMSO or with Mdivi-1 (20 μM). All quantitation were normalized to the protein level of endogenous parental GAPDH. B Cell colony formation assay of AN3 CA cells with FBXO7 knockout or parental, and treated with DMSO or with Mdivi-1 (20 μM; Left). Statistics of cell colony formation assay (Right). Data are shown as means ± SD (n = 3). *p < 0.05, **p < 0.01. C Cell proliferation assay of AN3 CA cells with FBXO7 knockout or parental, and treated with DMSO or with Mdivi-1 (20 μM). Data are shown as means ± SD (n = 5). *p < 0.05. D Cell migration assay of AN3 CA cells with FBXO7 knockout or parental, and treated with DMSO or with Mdivi-1 (20 μM; Left). Statistics of cell colony formation assay (Right). Data are shown as means ± SD (n = 3). *p < 0.05, **p < 0.01. E A model proposed according to the findings of the present study. I: Under physiological conditions, FBXO7-WT promptly degrades INF2 via UPS to prevent ECa. II: ECa-associated FBXO7 mutants are defective in the degradation of INF2 and ECa-associated INF2 mutants escape from the regulation by FBXO7, leading the INF2 accumulation and triggering the INF2-associated mitochondrial division, leading to ECa. Considering the FBXO7-INF2-DRP1 cascade, applying of Mdivi-1 may suppress proliferation and migration, and promote apoptosis of ECa cell lines with FBXO7 deletion and mutations. Experiments in (A) were repeated three times.