2003 Volume 43 Issue 4 Pages 307-313
Objective. Cremophor EL (polyoxythylene caster oil), used as a solvent for cyclosporin A, was investigatedto determine whether it enhances the effects of cell-killing by etoposide (VP-16) in human lung carcinomacells in vitro. Methods. Survival fractions were measured by in vitro growth inhibition assay in PC-14 (human adenocarcinoma), KB (human epidermoid carcinoma), H69 (human small cell lung carcinoma) cells. The results were also confirmedby in vitro clonogenic assay in PC-14 cells. The intracellular accumulations of [3H] VP-16 were counted with a liquidscintillation counter in PC-14, KB, H69 and A549 (human adenocarcinoma) cells. The expression of MDR1 genemRNA was measured by real-time quantitative PCR assay. Results. In PC-14 cells, 250 μg/ml of Cremophor EL enhancedthe VP-16 sensitivity by over 102 times in clonogenic assay without obvious cell damage by itself. The intracellularaccumulation of VP-16 was enhanced by Cremophor EL in both PC-14 and A549 cells, but not in KB or H69. AlthoughCremphor EL has ben known to reverse the multidrug resistance (MDR) phenotype, we did not detect the MDR genen PC-14 and A549 cells. Conclusion. Cremophor EL enhances the effect of cell-killing by VP-16 in human lung adenocarcinomacells via enhancement of VP-16 influx, that is not related with the MDR reversal.
