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Vol.43 No.4 contents | Japanese/English |
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- Original Article -
Effect of Cremophor EL on Cell-killing by Etoposide in Human Lung Adenocarcinoma Cells
Toshio Sugane1, Ichiro Tsujino1, Tetsuo Yamazaki1, Noriaki Takahashi1, Tsuneto Akashiba1, Umihiko Sawada1, Takashi Horie11First Department of Internal Medicine, Nihon University School of Medicine, Japan
Objective. Cremophor EL (polyoxythylene caster oil), used as a solvent for cyclosporin A, was investigated to determine whether it enhances the effects of cell-killing by etoposide (VP-16) in human lung carcinoma cells 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 confirmed by in vitro clonogenic assay in PC-14 cells. The intracellular accumulations of [3H] VP-16 were counted with a liquid scintillation counter in PC-14, KB, H69 and A549 (human adenocarcinoma) cells. The expression of MDR1 gene mRNA was measured by real-time quantitative PCR assay. Results. In PC-14 cells, 250 μg/ml of Cremophor EL enhanced the VP-16 sensitivity by over 102 times in clonogenic assay without obvious cell damage by itself. The intracellular accumulation of VP-16 was enhanced by Cremophor EL in both PC-14 and A549 cells, but not in KB or H69. Although Cremophor EL has been known to reverse the multidrug resistance (MDR) phenotype, we did not detect the MDR gene in PC-14 and A549 cells. Conclusion. Cremophor EL enhances the effect of cell-killing by VP-16 in human lung adenocarcinoma cells via enhancement of VP-16 influx, that is not related with the MDR reversal.
key words: Cremophor EL, Etoposide (VP-16), Human lung adenocarcinoma cells, Effect of cell-killing, Multidrug resistance
Received: December 6, 2002
Accepted: June 2, 2003
JJLC 43 (4): 307-313, 2003
