Antiproliferative and Overadditive Effects of Everolimus and Mycophenolate Mofetil in Pancreas and Lung Cancer Cells In Vitro

Abstract 

Background

Everolimus inhibits the growth of several tumor cell lines in vitro as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line Panc-1 and on a small cell lung cancer cell line ScLc.

Materials and Methods

Cells were cultured under standardized conditions. Everolimus was added in increasing doses from 0.005 to 500 μg/mL; MMF was used from 0.05 to 5000 μg/mL. For co-incubation experiments, we combined everolimus (0.005 μg/mL and 0.05 μg/mL) with five concentrations of MMF; and MMF (0.5 μg/mL and 5 μg/mL) with five concentrations of everolimus. The antiproliferative capacity was assessed by a BrdU incorporation assay.

Results

Everolimus and MMF inhibited BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50% inhibition was seen in Panc-1 only at 50 μg/mL everolimus, but in ScLc at 5 μg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was observed at 5 μg/L. In ScLc, 40% inhibition of BrdU incorporation was seen only at 50 μg/L MMF. In co-incubation, an effective combination for both Panc-1 and ScLc was 5 μg/mL MMF with 0.005 μg/mL everolimus resulting in 50% inhibition of BrdU incorporation (P < .001).

Conclusions

Everolimus and MMF showed dose-dependent antiproliferative effects in tumor cell lines in vitro both alone and in combination. The combined use of everolimus and MMF showed supra-additive effects at concentrations used for therapeutic immunosuppression in patients.