Objective        To determine the effects of estrogen activation in the G-protein coupled estr

ogen receptor (GPER) mediated-6/STAT3 (GPER/IL-6/STAT3) signaling pathway on the cell proliferation in breast cancer SKBR-3 cells.        Methods        17-β-estradiol (E

2

)

GPER specific agonist (G1)

GPER specific antagonist (G15)

human IL-6-neutralizing antibody (anti-IL-6) and STAT3 signaling specific inhibitor (cucurbitacin I

JSI-124) were used respectively to treat SKBR-3 cells. So the cells were accordingly assigned into the control group

E

2

treatment group

G1 treatment group

E

2

+G15 treatment group

G1+G15 treatment group

E

2

+anti-IL-6 treatment group

G1+anti-IL-6 treatment group

E

2

+JSI-124 treatment group and G1+JSI-124 treatment group. The content of IL-6 in the supernatant was detected by ELISA. CCK-8 assay was used to test the change of proliferate ability

and Western blotting to the protein expression levels of p-STAT3 and STAT3.        Results        E

2

and G1 significantly increased the content of IL-6 in the supernatant which could be blocked by GPER specific antagonist (G15) (P0.05). After treating with E

2

and G1 in the SKBR-3 cells

the cell proliferation was increased remarkably compared with control groups

with the relative cell amount of 1.68±0.13 and 1.74±0.21 times higher than those of the control groups (P0.05). However

the growth effects could be significantly blocked by G15 and anti-IL-6 (P0.05). E

2

and G1 enhanced the protein expression of p-STAT3 in 1

3

6

and 12 h after treatment

and the protein level reached the peak values at 12 h and 3 h respectively in E

2

treatment group and G1 treatment group

with the relative protein expressions of 2.54±0.23 and 3.12±0.24 times higher than those of the control groups. G15

anti-IL-6 and JSI-124 blocked the above changes (P0.05). Furthermore

JSI-124 also inhibited the growth effects induced by E

2

and G1 as well as G15 and anti-IL-6 (P0.05).        Conclusion        Estrogen activates the membrane estrogen receptor GPER to en

hance the autocrine secretion of IL-6 which activates its downstream STAT3 inflammatory signal pathway. Moreover

the GPER/IL-6/STAT3 signal pathway mediates the cell proliferation induced by estrogen.