MODULATION OF MDR1 mRNA EXPRESSION AND REVERSION OF MULTI-DRUG RESISTANCE BY PPMP IN KBv200 CELL LINE / 解放军医学杂志

ABSTRACT

The current study was designed to investigate the effects of PPMP (DL-threo-1-phenyl-2- palmitoylamino-3-morpholino-1-propanol), a kind of glycolipids synthase inhibitor, on the modulation of mdr1 mRNA expression and the reversing effect of multi-drug resistance by PPMP in human malignancy KBv200cell line. In vitro KBv200 cells were treated with PPMP in different concentration, the alterations of mRNA expression of drug-resistant gene mdr1 in KB (sensitive cell line) and KBv200 (before and after the treatment of PPMP) cells were analyzed by RT-PCR. Intracellular rhodamine(Rh123) concentration was measured by flow cytometry. PPMP was found to inhibit mdr1 gene expression of KBv200 at the mRNA level, and complete inhibition appeared at 25μmol/L PPMP treatment for 48h. PPMP could increase intracellular Rh123 accumulation in resistant cell lines. This modulation of gene expression and Rh123 accumulation was directly correlated with the concentration of PPMP. It suggested that PPMP, a chemical inhibitor of glycolipids synthase, could modulate mdr1 expression at the mRNA level in a content dependent manner, PPMP possesses MDR-reversing activity.