SP/NK‐1R promotes gallbladder cancer cell proliferation and migration
| العنوان: | SP/NK‐1R promotes gallbladder cancer cell proliferation and migration |
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| المؤلفون: | Xianxiu Ge, Lin Miao, Boming Xu, Si-Min Tang, Xueting Deng, Huishan Wang, Quanpeng Li, Peiyao Wu |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, substance P, Interleukin-1beta, Transplantation, Heterologous, Clone (cell biology), Mice, Nude, gallbladder cancer, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, In vivo, Cell Line, Tumor, Animals, Humans, RNA, Small Interfering, Receptor, Protein kinase B, NK‑1R, Cell Proliferation, Interleukin-6, Tumor Necrosis Factor-alpha, Chemistry, Cell growth, Akt, NF‐κB, Transcription Factor RelA, Cell migration, NF-κB, Original Articles, Cell Biology, Receptors, Neurokinin-1, 030104 developmental biology, Matrix Metalloproteinase 9, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Immunohistochemistry, Original Article, Gallbladder Neoplasms, Proto-Oncogene Proteins c-akt, Signal Transduction |
| الوصف: | Aberrant substance P/neurokinin‐1 receptor (SP/NK‐1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK‐1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK‐1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK‐1R. The results showed that SP and NK‐1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK‐1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF‐κB p65 and the tumor‐associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF‐κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF‐κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK‐1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF‐κB pathway. |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::316b628fce32aec7835e411404e9eb8b https://doi.org/10.1111/jcmm.14230 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....316b628fce32aec7835e411404e9eb8b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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