Preliminary studies on the mechanisms of a new anti-tumor agent PH II-7 with special preference to multidrug resistant tumor cells

Abstract

OBJECTIVE: To determine the anti-tumor activity of PH II-7 in vitro and explore preliminarily its mechanisms. METHODS: The anti-tumor activity was measured using colorimetric MTT assay. Apoptosis was determined with fluorescence-activated cell sorter (FACS), electron microscopy and agarose gel electrophoresis. The expressions of mdr1 and sorcin genes were determined by Northern blot assay. RESULTS: PH II-7 inhibited the proliferation of various human tumor cells derived from different tumor cell lines. The IC50 values varied from 0.34-18.61 mumol/L. Especially, PH II-7 had strong inhibitory effect on multidrug resistant tumor cells, whereas adriamycin (ADR) was resistant. Apoptosis was induced in HL60 and HL60/ADR cells treated with 1 microgram/ml PH II-7, while PH II-7 inhibited the expressions of mdr1 and sorcin genes. CONCLUSIONS: PH II-7 is a new potential agent which has strong inhibitory effect on both multidrug resistant cells and their parental cells. PH II-7 may increase the intracellular drug concentration in MDR cells by inhibiting the expressions of the MDR-related genes mdr1 and sorcin and induce the apoptosis of MDR cells and their parental tumor cells.