[Inhibitory effect of tirapazamine combined with phosphatidylinositol 3-kinase inhibitor LY294002 to ovarian cancer cells].
OBJECTIVE
To study the inhibitory effect of tirapazamine (TPZ) combined with LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), on the growth of human ovarian carcinoma cells.


METHODS
Human ovarian carcinoma cells of the line HO8910PM were cultured and treated with tirapazamine alone and treated with TPZ of different concentrations combined with LY294002 of the concentration of 50 micromol/L respectively under aerobic and hypoxic conditions. And human ovarian carcinoma cells of the line OVCAR-3 were cultured and treated with YPZ alone and treated with TPZ of different concentrations combined with LY294002 of the concentration of 25 micromol/L respectively under aerobic and hypoxic conditions. MTT method was used to detect the surviving fractions of these carcinoma cells.


RESULTS
The IC(50) values of TPZ on the HO8910PM cells under hypoxic condition was 40.6 micromol/L, significantly lower than that under aerobic condition (53.0 micromol/L, P < 0.01). The IC(50) values of TPZ on the OVCAR-3 cells under hypoxic condition was 65.9 micromol/L, significantly lower than that under aerobic condition (97.4 micromol/L, P < 0.01). The IC(50) value of TPZ combined with LY294002 on the HP8910PM cells under hypoxic condition was 22.7 micromol/L, significantly lower than that under aerobic condition (31.5 micromol/L, P < 0.01). The IC(50) value of TPZ combined with LY294002 on the OVCAR-3 cells under hypoxic condition was 49.1 micromol/L, not significantly different from that under aerobic condition (51.0 micromol/L, P > 0.05).


CONCLUSIONS
TPZ inhibits the growth of human ovarian carcinoma cells. The inhibitory effects of TPZ on the growth of human ovarian carcinoma cell of the lines HO8910PM and OVCAR-3 under hypoxic conditions are significantly higher than those under aerobic condition1. LY294002 increases the inhibitory effect of TPZ on the ovarian cancer cells, compared with TPZ treatment alone, TPZ combined with LY294002 decreases the IC(50) of HO8910PM and OVCAR-3 cells significantly.
Department of Molecular Pharmacology, Sichuan Tumor Hospital, Chengdu 610041, China.
Yuan
Y
Ren
Xiao
X
Zha
Guo-nan
GN
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D009025:Morpholines / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014227:Triazines; D000077704:Tirapazamine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one