[Reversal of multidrug resistance by cyproheptadine in KBV200 cells].

The cyproheptadine (CYP) reversal of multidrug resistance (MDR) and its mechanism in KBV200 cell line were studies. MTT assay showed that CYP 15.0 mumol.L-1 could reverse vincristine, adriamycin (ADR) and etoposide resistance in KBV200 cells by a factor of 5.5, 2.0 and 1.9, respectively. CYP appeared to have no influence on the cytotoxicity of 5-fluorouracil (5-FU) and melphalan (MEL) in the cells. These results indicate that CYP is a MDR reversing agent. CYP 15.0 mumol.L-1 increased the ADR accumulation in KBV200 cells from 0.68 +/- 0.03 microgram/10(6) cells to 1.36 +/- 0.08 micrograms/10(6) cells (P < 0.01). CYP 15.0 mumol.L-1 was shown to obviously increase rhodamine 123 (R123) accumulation in and decrease its efflux from the cells. There was no change in PGP dying intensity under immunocytochemical assay and in mdr1 RNA level through slot blot analysis in the KBV200 cells exposed continuously to CYP 15.0 mumol.L-1 for 72 h. These results suggest that CYP acts by inhibiting the pumping function of PGP.