Norcantharidin (NCTD) Regulates ER? Pathway And Tamoxifen Resistance Through MiR-873/CDK3

Objective: To explore the effect of NCTD on the growth of breast cancer cells and the regulation of tamoxifen resistance in breast cancer by a series of in vitro and in vivo exper iments.Methods: Our previous studies have known that the miR-873/CDK3 axis plays a key role in ER ? signal transduction and tamoxifen resistance.Since natural compounds have b ecome important sources of many clinically useful anticancer drugs,we tried to screen natu ral-derived compounds using real-time PCR for detection found NCTD can regulate miR-873 expression.to establish a cell model of breast cancer cell line MCF-7,ZR75-1 and tamox ifen resistant cells MCF-7/TamR to detect the effect of NCTD on miR-873,CDK3 expressi on in breast cancer cells by real-time western blotting.the effect of luciferase reporter gene analysis NCTD on ER ? transcriptional activity in breast cancer cells.The cell proliferatio n experiment was used to observe whether NCTD inhibited the cell proliferation of MCF-7and ZR75-1 cells,and whether NCTD treatment could make MCF-7/TamR cells sensitive to tamoxifen.a mouse model of breast cancer to explore the role of NCTD in tumor growth in nude mice.the plasmid transfection technique was used to further verify whether NCT D played a role in vitro and in vivo by targeting miR-873/CDK3.Results: Noregulin(NCTD)regulates the expression of miR-873/CDK3 in breast can cer cells,NCTD through miR-873/CDK3 regulation of ER ? signaling.NCTD inhibit cell g rowth in vitro and in vivo by targeting miR-873/CDK3.NCTD regulates tamoxifen resistan ce in breast cancer cells.Conclusions: in this study,we have demonstrated the role of NCTD in regulating ER signaling and tamoxifen resistance in human breast cancer cells via the miR-83/CDK3 axis.We found that:(i)NCTD increases miR-873 expression and inhibits CDK3 expression in MCF-7 cells;(ii)NCTD regulates ER? signaling via miR-873/CDK3(iii)NCTD inhibits ER signaling and breast cell growth via targeting miR-873/CDK3 in vitro and in vivo;(iv)NCTD treatment sensitizes resistant cells to tamoxifen though miR-873/CDK3 axis.Taken together,these findings support a key role for NCTD in regulating ER signaling and tamoxifen resistance in human breast cancer.