Expression And Effect Of Substance P And NK-1 In Colon Cancer

Objective 1.To study the expression of substance P (SP) and its receptor, neurokinin-1 (NK-1) in colon carcinomas and human colon cancer cell line RKO 2.Toevaluate the effect of potent selective NK-1 agonist [Sar9,Met(O2)11]substance P(SMSP) and selective antagonist L-733060 on human colon cancer cell line RKO in vitro.3. Toinvestigate the potential function of substance P and NK-1 in human colon cancer cellline RKO. Methods 1.The immunohistochemistry study was performed to detect theimmunolocation of substance P and neurokinin-1 in colon carcinomas (n=85). Several specimens were also selected to study as follows:normal colon specimens(n=13), adjacent specimens (n=22). hyperplastic polyps specimens (n=26), adenomas specimens (n=29).2. We carried out an in vitro immunocytochemical study to investigate the localization of substance P and NK-1 in RKO cells.3. various concentrations of SMSP (10-10M-10"6M) and L-733,060 (10-9M-10-5M) were applied alone in RKO cells. MTT assay were used to detect the cytoactivation. Resultsâ‘ We show here that colon carcinoma could co-express both substance P and NK-1.. The immunopositive substance P cells were distributed diffusely and the majority of SP labeling was localized within the cytoplasma of colon carcinoma, showed a diffuse or nest-like cytoplasmic staining. However, NK-1 could be observed in both plasma membrane and/or cytoplasma.â‘¡Substance p and receptor neurokinin-1 were also distributed in the cytoplasm in normal colorectal mucosal specimens, hyperplastic polyp, colon adenoma and adjacent specimens on cytoplasm.â‘¢. In RKO cells, we found immunoreactive substance P was mainly presented on cytoplasm and NK-1 on both membrane and plasma.â‘£.At a concentration of 10-8M SMSP exerted maximum proliferation action and L-733,060 (10-10-10-6M) inhibited cell growth in a dose dependent manner. Conclusion 1.Given that both colon carcinoma tissues and RKO cell line bear over expression of substance P and NK-1, it is suggested that neuroendocrine mechanisms participate the development of colon carcinoma.2. L-733,060 could blunt cell growth via NK-1 in vitro.3. Substance P may stimulate cell proliferation through NK-1 in vivo; NK-1 may serve as a critical gate to regulate substance P related cell proliferation and a new target for therapy.