To901317Inhibits The Proliferation Of MCF-7Human Breast Cancer Cells By The Pathway Of LXRα/NF-κB P65/CyclinD1

ObjectiveTo explore the anti-proliferative mechanism on TO901317, one of the syntheticagonists of liver X receptors (LXRs), in MCF-7human breast cancer cells and toprovide the new idea for the molecular targeted therapy for the breast cancer in thefuture.MethodsFirstly, MCF-7cells were treated with TO901317of different concentration fordifferent time and the proliferation of MCF-7cells were detected by MTT assay. Atthe same time, the effect of the cell cycle in MCF-7cells were analyzed by flowcytometry, and the protein expression of LXRα, LXRβ, NF-κB p65and cyclinD1were detected by western blot.Secondly, the technology of RNA interference was used to make LXRαexpression silenced in MCF-7cells, then the proliferation of MCF-7cells wereexamined by MTT assay, and the protein expression of LXRα, NF-κB p65andcylinD1were observed by western blot and immunofluorescence.Thirdly, Pyrrolidinedithiocarbamic acid (PDTC), one of NF-κB inhibitors, beingused, MTT assay was used to measure the effect of PDTC on the proliferation ofMCF-7cells and the change of LXRα, NF-κB p65and cyclinD1expression weremeasured by western blot. ResultsThe results showed:1. TO901317could gradually suppress the cell proliferation obviously. What’smore, TO901317could be blocked from phase G1to phase S and the cell cycle wasarrested at phase G1. The protein expression of LXRα and LXRβ were graduallyincreased, while NF-κB p65protein expression was down-regulated as well ascyclinD1. The expression of I κBα showed a complementary tendency with NF-κBp65, which further proved TO901317could inhibit the protein expression of NF-κBp65.2. LXRα siRNA transfected by liposome into MCF-7cells could significantlydown-regulate LXRα expression at mRNA and protein level, and delay the effect ofTO901317on inhibiting the cell proliferation, increasing LXRα expression anddecreasing NF-κB p65and cyclinD1expression in MCF-7cells.3. PDTC could enhance the inhibitory effect of the cell proliferation ofTO901317and down-regulate NF-κB p65and cyclinD1expression. But there was nosignificant effect on the expression of LXRα. All above suggested the interactionbetween LXRα as the upstream of the pathway and NF-κB p65taken as thedownstream.Conclusions1. TO901317could down-regulate the protein expression of NF-κB p65inMCF-7human breast cancer cells.2. TO901317could inhibit the proliferation of MCF-7cells through activatingLXRα, down-regulating NF-κB p65and cyclinD1expression.