Objective      To investigate whether PAQR3 can enhance the chemosensitivity of breast cancer line to epirubicin

and the possibly underlying mechanisms.       Methods      The mRNA level of PAQR3 in 4 breast cancer cell lines (MDA-MB-231

MCF7

SK-BR-3 and T47D) with different statuses of ER

PR and HER2 receptors were analyzed by real-time PCR. The plasmid pEGFP-PAQR3 encoding full-length

sequence of PAQR3 was transfected into the SK-BR-3 cells

and the cells transfected with empty vector pEGFP-C1 served as control. The inhibitory ratio and IC

50

of epirubicin on the SK-BR-3 cells were observed and compared. Flow cytometry was used to analyze the cell apoptosis

and Western blotting to detect the expression of apoptosis-related genes.       Results      Among the 4 breast cancer cell lines

MDA-MB-231 cells who were positive to the above 3 receptors expressed the highest level of PAQR3

while the SK-BR-3 and MCF7 cells got the relatively lower levels. After transfected with plasmid pEGFP-PAQR3

the SK-BR-3 cells become more sensitive to epirubicin as compared to those transfected with pEGFP-C1 (

P

0.05)

and their IC

50

was obvious decreased (25.33±0.94 vs 17.72±1.11 μg/mL

P

0.05). PAQR3 transfection had no effect on cell apoptosis (

P

0.05)

but when the cells were treated with the same doses of epirubicin

the expression of cleaved caspase-7 was significantly elevated in SK-BR-3 transfected with PAQR3

which contributed to the enhanced sensitivity to epirubicin. Nevertheless

no change of cleaved caspase-3

Bcl-2

and Bcl-xL was found. Furthermore

the anti-apoptotic activation of ERK by epirubicin was suppressed in SK-BR-3 transfected with PAQR3 compared with those transfected with empty vector

which explained their enhanced sensitivity to epirubicin.       Conclusion      PAQR3 enhances the chemosensitivity of breast cancer cells to epirubicin. In light of certain clinical findings

PAQR3 may be relative to the sensitivity of breast cancer to epirubicin.