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 OICR-9429 manufacturer mediate cell mitogenesis through NK-1 activation , 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-1 Target Selective Inhibitor high throughput screening are reported in humans, full-length (NK1-FL) and truncated (NK1-Tr). The cytoplasmic end of NK1-Tr lacks 100 residues, a region that functions as the substrate for G protein-receptor kinase . By in situ hybridization, the existence of NK-1 mRNA
has been demonstrated in malignant breast tissue but not detected in benign tissue . Western blots showed coexpression of NK1-Tr and NK1-FL in several different breast cancer cell lines, including T47D . Moreover, Previous RT-PCR study showed T47D cells contain more abundant NK-1 and substance P than others . Both NK1-Tr and NK1-FL can activate PKC through incorporating G proteins, which has been suggested as a potential cancer target [13, 14]. Recently, the expression of NK-1 in human Tipifarnib ic50 tumors has been investigated using immunohistochemistry . In several cell types, tumor cells bear more NK-1 than normal cells. These findings suggest that NK-1 may Dimethyl sulfoxide serve as a specific
factor involved in the development of breast cancer. However, it is unknown the exact cellular location of NK-1 in breast cancer cells. Although earlier in vitro studies have demonstrated that NK-1 antagonists could inhibit the growth of certain tumor cells in presence or absence of apoptosis [2, 3, 15–22], no study has been carried out on the antitumor action of specific NK-1 antagonist SR140333 in human breast cancer. Furthermore, it is also unclear whether the NK-1 specific agonist SMSP exerts proliferation promoting action or not in breast cancer cells. Therefore, in this study, we first generated an immunohistochemical study to investigate the immunolocation of NK-1 on breast cancer tissues and T47D cell line. Then we examined the effect of SMSP and SR140333 on in vitro growth of human breast cancer cell line T47D and further detected whether the NK-1 receptor antagonist SR140333 produce apoptosis in this cell line. Our study may enable us to develop a potential therapeutic target for breast cancer therapy.