The Influence Of Mammalian Tachykinin R/mHK-1, HHK-1 And HHK-1 (4-11) On Breast Cancer Cells And Angiogenesis

Rat/mouse Hemokinin-1(r/m HK-1), human Hemokinin-1(hHK-1) and human Hemokinin-1(4-11)[h HK-1(4-11)] which are belonged to tachykinin family were discovered about ten years ago. Meantime, we used substance P as one of classical tachykinins which people have already done a lot of research. We used three breast cancer cell lines (respectively, T-47D, MCF-7, MDA-MB-231) in which tachykinin NK1 receptor is highly expressed, and found that the four peptides SP,r/mHK-1,hHK-1,hHK-1(4-11) stimulated three breast cancer cells to proliferate significantly through their receptor NK1, and this proliferation was completely antagonized by NK1 receptor antagonist L732,138. Meanwhile,We found that the four peptides SP、r/mHK-1、hHK-1、hHK-1(4-11) had significant role in promoting angiogenesis on chick embryo chorioallantoic membrane(CAM), also this effect was antagonized by NK1 receptor antagonist L732,138.Our results indicated:(1) After SP,r/mHK-1,hHK-1,hHK-1(4-11) with three types of breast cancer cells (respectively,T-47D,MCF-7,MDA-MB-231) were incubated for 72 hours, the four peptides stimulated three breast cancer cells to proliferate, in details:in T-47D, SP,r/mHK-1,hHK-1,hHK-1(4-11) in 50nM showed the most significant effect; in MCF-7, SP,r/mHK-1,hHK-1,hHK-1 (4-11) in 100nM showed the most significant effect; in MDA-MB-231, SP,r/mHK-1,hHK-1 in 10nM showed the most significant effect, hHK-1(4-11) in 100nM showed the most significant effect. We found that each of the four peptides on three types of cells showed bell-shaped dose-response curves. After using the antagonist L732,138, the proliferation of three breast cancer cells was significantly antagonized similar to negative control. (2) we found that SP,r/mHK-1,hHK-1,hHK-1(4-11) in luM significantly promoted angiogenesis on chick chorioallantoic membrane, especially promote the numbers of 3rd vessels and the bed area of capillary. After using the antagonist L732,138, the effect of SP, r/mHK-1, hHK-1, hHK-1 (4-11) in the chick chorioallantoic membrane angiogenesis was antagonized in varying degrees similar to negative control. Thus, we proved HK-1, primarily through its receptor NK1 promoted breast cancer cell proliferation and angiogenesis.