【Objective】 To identify the molecular mechanisms by which fisetin inhibited cell proliferation and induced apoptosis in Hela cells. 【Methods】 Hela cells were treated with fisetin

and the effect of fisetin on cell growth and apoptosis was observed by MTT

PI

and Annexin V. The expression level and activity changes of apoptotic key proteins

caspase

and Apaf-1

the phosphorylated level of ERK1/2

and the expression of COX-2 and PGE2 were detected by Western blot

RT-PCR

immunofluorescence imaging

respectively. The inhibition by siRNA or inhibitors was used to confirm the function of above key proteins in fisetin-mediated antitumor effects. 【Results】 Fisetin

with a concentration of 80-200 ?滋mol/L

inhibited the proliferation at a rate of 20% to 48% and with a concentration of 100-200 ?滋mol/L

induced apoptosis of Hela cell. It increased the activities of Caspase-3 and Caspase-9 at ranges of 20% ~ 50% and 22% ~ 38%

respectively

induced Apaf1 protein expression and cytochrome-C release. With the increase of the dosage

Fisetin inhibited the phosphorylation of ERK1/2 protein of the ERK MAPK signaling pathways. Combined with the ERK inhibitor or siRNA

it suppressed the proliferation at a rate of 60% to 70% and COX-2 protein expression of the Hela cell. Also

it reduced PGE2 production to 1800 pg/mL-2600 pg/mL and abrogated the binding of p300

NF-κB

p50

and p65 to COX-2 promoter. Compared with the control groups

these differences were significant (P < 0.05).【Conclusions】 Fisetin induced apoptosis and proliferation inhibition by modulating the Apaf-1

ERK

and COX-2-dependent mechanisms in Hela cell.