Table 1.

Effects of rapamycin, bevacizumab, and BEV/RAPA on body weight, i.p. tumor burden, ascites formation, cell proliferation, microvessel density, VEGF expression, and apoptosis of OV-90 and SKOV-3 ovarian cancer cells

Ovarian cancer cellsTreatmentsBody weight (g)No. i.p. tumor/mouseI.p. tumor burden (mg)Ascites formation
Microvessel densityKi-67 index (%)Cleaved caspase-3 (%)VEGF expression
Incidence (%)Volume (mL)
OV-90Vehicle24.6 ± 1.316 ± 8a2,610 ± 306a10/10 (100)5.8 ± 2.216.8 ± 3.2a28.6 ± 3.9a2.1 ± 0.9Strong
Bevacizumab22.4 ± 1.110 ± 3a459 ± 72b0/10 (0)ND6.3 ± 2.7b9.5 ± 2.1b3.4 ± 0.8Strong
Rapamycin24.9 ± 1.211 ± 4a664 ± 90b1/10 (10)0.58.4 ± 1.9b14.6 ± 3.1b2.8 ± 0.8Average
BEV/RAPA24.3 ± 1.35 ± 3b176 ± 29c0/10 (0)ND4.2 ± 1.0b4.2 ± 1.8c3.6 ± 0.9Weak
SK-OV3Vehicle24.4 ± 0.915 ± 6a1,863 ± 290a9/9 (100)5.6 ± 1.914.1 ± 2.9a21.6 ± 3.8a4.5 ± 0.8Average
Bevacizumab22.4 ± 1.19 ± 3a867 ± 128b0/9 (0)ND5.1 ± 1.3b9.9 ± 1.7b5.7 ± 0.9Average
Rapamycin23.8 ± 1.410 ± 3a968 ± 141b2/9 (22)0.5–0.78.0 ± 1.5c13.4 ± 2.1b4.1 ± 0.7Average
BEV/RAPA26.2 ± 0.84 ± 2b139 ± 48c0/9 (0)ND4.9 ± 1.4b5.4 ± 1.8c5.9 ± 1.2Weak
  • NOTE: Effects of rapamycin, bevacizumab, and BEV/RAPA on body weight at sacrifice, i.p. tumor burden, microvessel density, cell proliferation, ascites formation, VEGF expression, and apoptosis of OV-90 and SK-OV3 ovarian cells. Female SCID mice were i.p. injected with 5 × 106 OV-90 or SKOV-3 cells in 200 μL PBS. Mice bearing i.p. tumors were randomized to one of four treatment groups and each one was consisted of 14 mice. They were treated with vehicle, bevacizumab (5 mg/kg), rapamycin (1 mg/kg), or BEV/RAPA as described in Materials and Methods. Treatment started 2 wk after inoculation of tumor cells. Ascites formation was monitored thrice weekly. The mice were sacrificed and necropsied on day 50 after injection of tumor cells. By this time, the mice in the vehicle-treated group became moribund. The presence of ascitic fluid, macroscopic peritoneal tumor dissemination, and i.p. tumor burden was recorded. Mean vessel density, VEGF expression, Ki-67 index, and apoptosis in the tumors were determined by immunohistochemical staining with antibodies against CD31, VEGF, Ki-67, and cleaved caspase-3, respectively. VEGF expression was scored as described in Materials and Methods. Differences in i.p. tumor burden, microvessel density, percentage of Ki-67–positive cells, ascites formation, and percentage of cleaved caspase-3–positive cells between vehicle-, bevacizumab-, rapamycin-, and BEV/RAPA-treated groups were analyzed by ANOVA. Treatments with different letters are significantly different from one another (P < 0.01).