All-trans retinoic acid suppresses proliferation of breast cancer cells through DOK1/PPARγpathway / 中国病理生理杂志

ABSTRACT

AIM:To investigate the potential effect of all-trans retinoic acid (ATRA) on the proliferation of human breast cancer MCF-7 cells and its underlying mechanism.METHODS:Human breast cancer MCF-7 cells were in-cubated in DMEM supplemented with 10%fetal bovine serum and 1%penicillin/streptomycin.Western blot was performed to detect the protein expression and its phosphorylation.MTT assay and bromodeoxyuridine ( BrdU) incorporation, and TUNEL staining were carried out to determine the cell proliferation and apoptosis, respectively.Lentivirus carrying shRNA sequences targeting the gene of docking protein 1 ( DOK1 ) was used to silence DOK1 expression.The activity of peroxi-some proliferator-activated receptor gamma ( PPARγ) was measured using a PPARγtranscription factor assay kit.RE-SULTSATRA treatment suppressed the proliferation and promoted the apoptosis of MCF-7 cells.ATRA was also found to induce DOK1 expression in a time-dependent manner.Silence of DOK1 mitigated anti-cancer effect of ATRA evidenced by recovered the cell proliferation and reduced the cell apoptosis.In addition, DOK1 knockdown inhibited PPARγexpression and activity.Furthermore, inhibition of PPARγwith its specific inhibitor GW9662 attenuated impacts of ATRA on the cell proliferation and apoptosis.CONCLUSION: ATRA suppresses MCF-7 cell survival through inhibiting cell proliferation and promoting cell apoptosis, which is mediated by DOK1-activated PPARγ.