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

Transplant Proc. 2004 May;36(4):934-7. doi: 10.1016/j.transproceed.2004.03.126.

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 < or =.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.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Cyclosporine / therapeutic use*
  • Drug Therapy, Combination
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Rats
  • Rats, Wistar
  • Sarcoma, Experimental / drug therapy*
  • Sarcoma, Experimental / pathology*
  • Sirolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Sirolimus