Abstract:
Objective To study the pro-apoptotic effects of 1,25 dihydroxyvitamin D
3 in combination with Tamoxifen on MDA-MB-231 cells transfected with ERαexpression vector containing VDRE elements and associated molecular mechanism.
Methods To clone the 4×VDRE-Tk sequence of VDRE-pGL3 reporter vector into ERα/pcDNA 3.1+vector and to transfect it into MDA-MB-231 breast cancer cells.Moreover,to treat MDA-MB-231
VORE-ERα breast cancer cells with 1,25 dihydroxyvitamin D
3 and Tamoxifen to observe their pro-apoptotic effects as detected by TUNEL and to explore the expression and nuclear translocation of NFκB P65 subunit by western blot assay.
Results Compared with control group,the percentage of apoptotic cells increased remarkably after treatment with 1,25 dihydroxyvitamin D
3 and Tamoxifen for 72h.Also,1,25 dihydroxyvitamin D
3 and Tamoxifen synergistically inhibited the expression and nuclear translocation of NFκB P65 subunit as compared with control group.
Conclusion ERα-negative breast cancer cells with exogenous VDRE-Tk-ERα vector could effectively obtain responsiveness to Tamoxifen under the induction of 1,25 dihydroxyvitamin D
3,which in combination with Tamoxifen could synergistically induce apoptosis by influencing the expression and activity of NFκB P65 subunit.