Figure 7

Simvastatin inhibited HepG2 tumor growth in xenograft mice. HepG2 tumor-bearing BALB/c nude mice were divided into control and simvastatin treatment groups. The mice were treated with saline or 20 mg/kg body weight simvastatin twice a day by intraperitoneal (i.p.) injection. (a) Tumor tissues from the saline and simvastatin treatment groups were harvested at 14 days after injection. These tissues were isolated from each mouse after killing. (b) Tumor growth curves derived from nude mice in the saline- and simvastatin-treated groups. The tumor volumes of the nude mice were calculated twice a day for 2 weeks. (c) The tumor weights of the nude mice were measured after killing. Results are shown as the mean±S.E.M (n=12). Saline-treated mice compared with simvastatin-treated mice. ***P<0.001 (d) IHC analysis using antibodies against human p21, p27, Skp2, p-AMPK and p-STAT3 in the tumor tissues of the saline- and simvastatin-treated groups. All scale bars are 50 μm. (e) To summarize the in vitro and in vivo results of this study, we found that simvastatin promoted G0/G1 cell cycle arrest by increasing p21 and p27 expression via AMPK pathway activation and STAT3/Skp2 pathway suppression, respectively. These phenomena were dependent on inhibiting the production of mevalonate by simvastatin treatment in the HCC model