Figure 6

Simvastatin more significantly inhibited tumor growth in RB-depleted tumors than in RB-proficient tumors in vivo. (a) Simvastatin inhibited tumor growth in primary tumor. The B16 cancer cell xenograft model was established by subcutaneously injecting 1 × 10⁶ B16 cells into C57 mice. Then the mice were given ddH₂O or 60 mg/kg/day Simvastatin by gavage until the tumor sizes were more than 4 mm × 4 mm. Tumors were taken after 10 days and images were presented. Simvastatin inhibited tumor size and weight. Tumor weight (b) was evaluated 10 days after treatment and tumor volumes (c) were recorded every 2 days. (d) Simvastatin inhibited MCM7 and RB expressions in vivo. Tumor specimens were analyzed by immunohistochemical staining with MCM7 or RB antibodies. (e) Statistical difference of the number of MCM7-positive cells and RB-positive cells between control and drug-treated group. (f) RB-depleted tumors were more sensitive to Simvastatin. Nude mice bearing SiHa (cells infected with Adcon or AdE7 for 48 h) human cervical tumor xenografts were treated with ddH₂O or Simvastatin (30 and 60 mg/kg/day of body weight) through taking gavage. Taken the tumors after 12 days and imaged in figures are shown. Simvastatin more notably inhibited the tumor size and weight in RB-negative tumor than in control tumor. Tumor weight (g) was evaluated 12 days after treatment and tumor volume (h) were recorded every 2 days. (i) Simvastatin inhibited MCM7 and RB expressions in RB-negative tumor. Tumor specimens were analyzed by immunohistochemical staining with MCM7 or RB antibodies. (j) The statistics of MCM7-positive cells and RB-positive cells between control and drug-treated group. (k) Schematic model. Stains suppress MCM7 and RB protein expressions via activating ER stress and autophagy signaling pathway. The deficiency of MCM7 and RB protein induces chromosome instability, and gives rise to apoptosis in various tumor cells