Objective      To investigate the role of platelet-derived growth factor receptor-beta (PDGFR-β) signals in doxorubicin (Dox) resistance of triple-negative breast cancer cell line MDA-MB-231

and explore its underlying mechanism.       Methods      The percentage of cells arrested at G

2

phase

cell apoptosis and

viability were detected by flow cytometry and MTS assay in PDGF-DD (a PDGFR-β specific ligand) incubated cells. The expression levels of mutant p53 (mtp53)

cdk1

PDGFR-β

p21

bax

hsp90 and TopBP1 were determined by qPCR and Western blotting for the effects of PDGF-DD and Wortmannin (a PI3K inhibitor) on the mtp53 expression and its functions. qPCR was used to measure the mRNA levels of resistant genes in cells treated with p53 siRNA or (and) PDGF-DD.       Results      PDGF-DD significantly enhanced the cell viability

reduced the apoptotic rates and relieved G

2

/M cell cycle arrest in the MDA-MB-231 after Dox treatment. It greatly improved the protein level of mtp53 and seriously altered the expression levels of its downstream genes

cdk1

PDGFR-β

p21 and Bax

but showed negligible change of mtp53 mRNA (P0.05). Meanwhile the elevated mRNA and protein levels of hsp90 (a mtp53 protein-stabilizing factor) and topoisomerase (DNA) Ⅱ binding protein 1 (TopBP1

a mtp53 function-promoting protein) induced by PDGF-DD heavily decreased after Wortmannin treatment. Moreover

the improvement of the mRNA levels of resistant genes

FOXC2

twist

snail

nanog and oct4

induced by PDGF-DD were seriously limited via knocking down mutant p53.       Conclusion       PDGF-DD/PDGFR-β induces Dox resistance in MDA-MB-231 cells by stabilizing mtp53 protein and promoting mtp53-mediated resistance via up-regulating hsp90 and TopBP1 at transcriptional level through the PI3K signaling pathway.