Fig. 8 SQLE inhibitor terbinafine suppresses NAFLD-HCC growth in vitro and in vivo. SQLE inhibitor terbinafine suppresses NAFLD-HCC growth in vitro and.

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Presentation transcript:

Fig. 8 SQLE inhibitor terbinafine suppresses NAFLD-HCC growth in vitro and in vivo. SQLE inhibitor terbinafine suppresses NAFLD-HCC growth in vitro and in vivo. (A) Terbinafine treatment suppressed cell growth (left) and colony formation (right) in NAFLD-HCC (HKCI2, HKCI10) and HepG2 cell lines (n = 3, performed in triplicate). (B) Terbinafine suppressed SQLE expression and reversed the silencing of PTEN, as determined by Western blot (n = 3, performed in triplicate). (C) Terbinafine reduced the amounts of free cholesterol and cholesteryl ester in HCC cell lines (n = 4, performed in triplicate). (D) Terbinafine (80 mg/kg per day, oral) inhibited growth of subcutaneous HepG2 xenografts, as evidenced by reductions in tumor volume and weight. (E) Terbinafine increased the survival of mice harboring HepG2 xenografts. Kaplan-Meier analysis and log-rank test were used. (F) Terbinafine (80 mg/kg per day, oral) attenuated the growth of orthotopic HKCI2 xenografts. Both tumor volume and weight were reduced. (G) Terbinafine decreased the amounts of free cholesterol and cholesteryl ester in HepG2 xenografts and HKCI2 orthotopic nude mouse model. (H) Terbinafine (80 mg/kg per day, oral) suppressed tumorigenesis in DEN-injected and HFHC diet–treated Sqle tg mice (left), in terms of both tumor incidence and tumor number (right). (I) H&E and Ki-67 staining of vehicle and terbinafine-treated livers. The red arrows show the positive cells. Scale bars, 100 μm (H&E) and 50 μm (Ki-67). (J) Terbinafine treatment decreased liver/body weight ratio (left), liver and serum cholesterol concentrations (middle), and NADP+/NADPH ratio (right). (K) Representative Western blot analysis showed that terbinafine suppressed Sqle expression and reversed the effect of SQLE on downstream factors DNMT3A and PTEN. Data are means ± SEM. The significance of the difference between cell growth rates and tumor growth rates in nude mice was determined by repeated-measures ANOVA. Mann-Whitney U test was used for comparing means between two groups. *P < 0.05, **P < 0.01, ***P < 0.001. Dabin Liu et al., Sci Transl Med 2018;10:eaap9840 Published by AAAS