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The NK1 Receptor Antagonist NKP608 Inhibits Proliferation of Human Colorectal Cancer Cells via Wnt Signaling Pathway

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The NK1 Receptor Antagonist NKP608 Inhibits Proliferation of Human Colorectal Cancer Cells via Wnt Signaling Pathway

Xiao-Ling Niu et al. Biol Res.

Abstract

Background: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism.

Methods: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot.

Results: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, β-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3.

Conclusions: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/β-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.

Keywords: Colorectal cancer; NKP608; Proliferation; Wnt signaling pathway.

Figures

Fig. 1
Fig. 1
NKP608 inhibited HCT116 cells proliferation. a OD values of HCT116 cells were inhibited by NKP608 with a concentration-dependent manner while those of normal cells were not. b HCT116 cells were treated with NKP608 for 24, 48, 72 h and cell viability was quantified by CCK8 assay. Values are expressed as mean ± SD. *p < 0.05 versus without NKP608 groups. *p < 0.05 versus NC groups (with 1‰ DMSO)
Fig. 2
Fig. 2
NKP608 attenuated the HCT116 cells migration and invasion ability through transwell chamber invasion/migration assay. a Images showing that the invasive cells treated with 24 h incubation of NKP608 were significantly reduced compared with the NC group. b Images showing that the migrated cells treated with 24 h incubation of NKP608 were significantly reduced compared with the NC group. Data of the average number of cells were from three independent experiments. *p < 0.05 versus NC group
Fig. 3
Fig. 3
NKP608 causes inhibition of in HCT116 cells. a HCT116 cells apoptosis was tested by flow cytometric analysis after Annexin V-FITC/PI staining, and apoptotic cells (Annexin V+PI and Annexin V+PI+) were shown. b Effect of NKP608 on the expression of Bax, Bcl-2 and Caspase-3 protein were detected by western blot assay. c Representative western blot images are shown. Values are expressed as the mean ± SD (n = 3). *p < 0.05 versus NC group
Fig. 4
Fig. 4
NKP608 inhibited Wnt/β-catenin signaling pathway in colorectal cancer cells. a Western blot revealed that NKP608 resulted in an inhibitory action of Wnt relative proteins and proteins relevant cell growth including β-catenin, Wnt-3a, E-Cadherin, Cyclin D1 and VEGF. b Quantitative expression levels of proteins are shown. Values are expressed as the mean ± SD (n = 3). *p < 0.05 versus NC group

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