ABSTRACT
Objective To investigate the effect of 5-Aza-CdR on experimental lung metastasis of breast cancer and the possible mechanisms.Methods MDA-MB-231 cells were divided into control group and 5-Aza-CdR-treated group.The mRNA expressions and promotor methylation status of BRMS1 and CXCR4 of the MDA-MB-231 cells were evaluated by SqRT-PCR and MSP respectively.Then,the MDA-MB-231 cells of control group and 5-Aza-CdR-treated group were injected into BALB/c nude mice through lateral tail veins,respectively.five weeks later,the mRNA abundance of the target gene HPRT and internal control gene GAPDH of the lung tissues from the mice were evaluated by FqRT-PCR.Results 5-Aza-CdR upgraded the BRMS1mRNA expression significantly than that in control group(0 versus 0.39?0.001,P0.05) and the status of unmethylated CXCR4 CpG island 1 in promotor were not changed significantly.The Ct values of HPRT and GAPDH in control and 5-Aza-CdR-treated groups were 24.75?1.55,16.19?0.69 versus 27.61?1.67,17.48?0.96 respectively,2-??Ct=0.34.The mRNA abundance of the HPRT was lower and there were fewer metastases in the lungs of 5-Aza-CdR-treated group compared with control group.Conclusions 5-Aza-CdR can activate tumor metastasis suppressor gene BRMS1 by demethylation mechanism,and thus,decreased the ability of breast cancer MDA-MB-231 cells for experimental metastasis to lungs.