THE SYNERGISTIC EFFECTS OF 1?-25-DIHYDROXY VITAMIN D_3 AND TAMOXIFEN ON ER-NEGATIVE BREAST CANCER CELLS CONTAINING EXOGENOUS PVDRE-TK-ER? PLASMID IN VIVO / 营养学报

ABSTRACT

Objective:To observe the inhibitory effects of VD3 and Tamoxifen on ER-negative breast cancer cells transfected with human recombinant pVDRE-Tk-ER? eukaryotic expression plasmid in vivo. Method:A recombinant human ER? expression plasmid containing 4 copies of VDRE and Tk promoter was introduced into the ER-negative MDA-MB-231 breast cancer cell. The transformed breast cancer cells were inoculated into athymic nude mice. 4 w after tumor inoculation,mice bearing the tumor of approximately 200 mm3 were treated with 0.5?g/kg of VD3 and/or 50mg/kg of Tamoxifen(SC) for 20d. The tumor volume was precisely measured,concurrently HE stain and Ki-67 immunohistochemical(IHC) assay were performed to detect the anti-proliferative effect of Vit D3 in combination with Tamoxifen in vivo. Results:After 20d of treatment,VD3 and Tamoxifen synergistically decreased the tumor volume as compared with control group. And the IHC results also showed that the Ki-67 expression was significantly inhibited by co-treatment of VD3 and Tamoxifen,which means the arrest of cell cycle progression. Conclusion:VD3 could effectively restore the sensitivity of ER-negative breast cancer cells to Tamoxifenby inducing the expression of exogenous ER? gene through the VDRE and Tk promoter in vivo.