Rapamycin even when combined with cyclosporine attenuates tumor growth but does not induce regression of established walker sarcomas

Abstract

Purpose To investigate the effect of rapamycin (Rapa) on growth or regression of Walker tumor used alone or in combination with CsA and MMF. Methods and results Wistar rats received water (control) or Rapa or CsA 1 day before and daily after tumor inoculation. On day 10, tumor volume (TV) was smaller among Rapa (6.8 ± 2.7 cm 3) versus control (14.9 ± 4.2 cm 3, P < .001) or CsA (13.9 ± 3.0 cm 3, P < .0001) treatment groups. Tumor growth was greatly inhibited (TI) by Rapa (−49.3%). Tumor weight (TW) was significantly ( P ≤ .001) lower in Rapa (3.7 ± 1.2 g) versus CsA (8.8 ± 2.1 g) or control (7.3 ± 2.0 g) animals. An additional set of rats received water or Rapa or CsA + Rapa, or MMF + Rapa 1 day before tumor inoculation. On day 10, TV and TW were lower among Rapa (3.8 ± 1.5 cm 3) and Rapa + CsA (3.1 ± 1.2 cm 3) and Rapa + MMF (4.6 ± 2.7 cm 3) groups compared with controls (10.9 ± 3.8 cm 3, P < .0001). TI was −52.1% in Rapa, −68.5% in Rapa + CsA, and −63% in Rapa + MMF. A further set of rats received either water or Rapa on the day 4 after tumor inoculation. On day 10, tumor growth and TW among the Rapa and control groups were similar. Conclusion Rapamycin greatly inhibited tumor growth when used alone or with CsA or MMF, but did not produce an effect on a well-established Walker sarcoma.