SR140333 counteracts NK-1 mediated cell proliferation in human breast cancer cell line T47D

Immunohistochemical staining was carried out to investigate the immunolocation of NK-1 in breast cancer tissues and T47D cell line, thereafter, various concentrations of [Sar9, Met(O2)11]substance P and SR140333 were applied alone or combined. MTT assay was applied to detect cytoactivation and coulter counter was to detect growth curve. The Hoechst33258 staining was performed to detect apoptosis.We found that breast cancer and T47D cells bear positive expression of NK-1. SR140333 inhibited cell growth in a dose dependent manner. Furthermore, SR140333 could counteract [Sar9, Met(O2)11]substance P induced proliferation. Hoechst33258 staining revealed the presence of apoptosis after SR140333 treatment.Our study demonstrated SR140333 exert proliferation inhibition in breast cancer cell line T47D and indicates NK-1 play a central role in the substance P related cell proliferation in breast cancer.Breast cancer is the most common cancer among women worldwide. It already is an urgent public health problem in high-resource regions, and is becoming an increasingly urgent problem in low-resource regions, where incidence rates have been increasing by up to 5% per year [1]. Despite earlier radiological examination, complete surgical resection and aggressive chemotherapy, it is still a social dilemma. Research studies have shown relevance of neuroendocrine molecules in breast cancer development, such as substance P and its receptor, NK-1, which belongs to G protein coupled receptor [2,3]. Substance P is a member of neurokinin family. Pharmacological studies have confirmed NK-1 as the high affinity receptor of substance P. It is well known that substance P and NK-1 are widely expressed in neural and non-neural sources [4-11]. Moreover, substance P could mediate cell mitogenesis through NK-1 activation [7], and using specific NK-1 antagonists (such as CP-96345, C-99994) in breast cancer cell lines could blunt the autocrine and/or paracrine cell proliferation [2,3].Two forms of NK-