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

Abstract

BackgroundIt has been demonstrated that certain NK-1 antagonists could reduce proliferation of several cancer cell lines, however, it is unknown whether SR140333 exerts proliferation inhibition in breast cancer cell line.MethodsImmunohistochemical 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.ResultsWe 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.ConclusionsOur 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.

Neurokinin-1 activation affects EGFR related signal transduction in triple negative breast cancer

“…ation and cell cycle of TNBC cells, which was in accordance with previous 351 studies[10,11]. An interesting observation was that the highest concen-352 tration (10 −5 M) of SMSP could not produce the strongest proliferation 353 stimulating effect.…”

NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer

“…Previous studies aimed at determining the effects of NK1 antagonist treatment on tumour cells in vitro have reported an inhibition of tumour growth, initiation of apoptosis, decreased migration and reduced cytokine secretion by tumour cells [31,38,41,42,46,47,66,70,72].The predominant effects of exogenous SP on tumour cells in vitro are mitogenesis, migration, cytokine secretion and chemotaxis [40,43,[73][74][75][76][77][78]. These effects are believed to be NK1 receptor dependent [70].…”

“…Recent studies have implicated SP in the proliferation and progression of many cancer types [36]. In cell culture studies, SP has consistently been shown to induce tumour cell mitogenesis, with NK1 antagonists causing apoptosis [31,[37][38][39][40][41][42][43][44] and decreased mitogenesis, particularly on NK1 receptor-expressing human cancer cell lines, whereas non-neoplastic cell lines did not show these effects [33]. Thus, it has been suggested that the NK1 receptor antagonist Emend may not only be useful in the treatment of chemotherapy-induced emesis, but may also inhibit SP-induced tumour cell proliferation.…”

“…Several studies have shown an increase in NK1 receptor expression in human surgical specimens of astrocytoma and brain metastases from breast carcinomas and melanoma [30][31][32][33][34][35]. Substance P (SP) is a proinflammatory tachykinin that acts preferentially on NK1 receptors.…”

An indirect role for the oncomir-519b in the expression of truncated neurokinin-1 in breast cancer cells

“…Furthermore, substance P can induce the production of cytokines to regulate NK1 expression [5]. Since NK1 antagonists are available, these drugs could be used to slow the transcriptional rate of NK1 as a method of BC treatment [18,26]. The findings in this report might not be limited to BC since NK1 has been linked to the development of various cancers [18,27–30].…”