[Preliminary studies on the mechanisms of a new anti-tumor agent PH II-7 with special preference to multidrug resistant tumor cells].
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.
Tan
Yao-hong
YH
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS, PUMC, Tianjin 300020, China.
Qi
Jing
J
Liu
Wei-jun
WJ
Yang
Chun-zheng
CZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal