Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling

Background: clinically,breast cancer is generally classified into estrogen receptor-positive (er+) or estrogen receptor-negative (er-) subtypes. the phytoestrogen calycosin has been shown to inhibit the proliferation of er+ cells,which may be mediated by a feedback loop that involves mir-375,ras dexamethasone-induced 1 (rasd1),and erα. however,how calycosin acts on er- breast cancer cells remains unclear. results: here,we show that calycosin inhibited the proliferation of both er- (mda-mb-468 and skbr3) and er+ breast cancer cells (mcf-7 and t47d) and that these inhibitory effects were associated with the up-regulation of the long non-coding rna (lncrna) wdr7-7. for the first time,we demonstrate that the expression of wdr7-7 is reduced in breast cancer cell lines and that the overexpression of wdr7-7 inhibits growth through a mechanism that involves g-protein coupled estrogen receptor 30 (gpr30). meanwhile,we show that calycosin stimulated the wdr7-7-gpr30 signaling pathway in mcf-7,t47d,mda-mb-468,and skbr3 breast cancer cells. in contrast,in mcf10a and gpr30-deficient mda-mb-231 cells,due to a lack of wdr7-7-gpr30 for activation,calycosin failed to inhibit cell growth. additionally,in all four gpr30-positive breast cancer lines,calycosin decreased the phosphorylation levels of src,egfr,erk1/2 and akt,but the inhibition of wdr7-7 blocked these changes and increased proliferation. in mice bearing mcf-7 or skbr3 xenografts,tumor growth was inhibited by calycosin,and changes in expression the levels of wdr7-7 and gpr30 in tumor tissues were similar to those in cultured mcf-7 and skbr3 cells. conclusions: these results suggest the possibility that calycosin inhibited the proliferation of breast cancer cells,at least partially,through wdr7-7-gpr30 signaling,which may explain why calycosin can exert inhibitory effects on er- breast cancer. © 2017 the author(s).