RESUMO
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.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Vesícula Biliar/metabolismo , Receptores da Neurocinina-1/metabolismo , Substância P/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias da Vesícula Biliar/genética , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Receptores da Neurocinina-1/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Transcrição RelA/metabolismo , Transplante Heterólogo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The purpose of this study is to investigate the mediating role of exercise value cognition between family function (FF) and exercise behavior and the moderating role of an only-child status. A questionnaire survey was conducted on 504 Chinese college students using the FF scale, the exercise value cognition scale, and the exercise behavior scale. The analysis yielded four main findings. (1) There are significant differences between an only-child and a non-only-child for negative exercise behavior and FF. The only-child group has a higher average FF score and a lower average negative exercise score. (2) Exercise behavior and four of its dimensions-exercise autonomy, attention control, exercise planning, and situational induction-are each significantly positively correlated with FF and exercise value cognition. (3) FF is a significantly positive predictor of exercise behavior, both directly and through exercise value cognition, which plays a partial mediating role. (4) Only-child status significantly moderates the mediating effect of exercise value cognition in the link between FF and exercise behavior. The intergroup differences mainly manifest in the influence of FF on exercise behavior and the influence of exercise value cognition on exercise behavior. In the only-child subsample, exercise value cognition plays a complete mediating role. The results of the current study demonstrated the important role that FF and exercise value cognition played in promoting the exercise behavior of college students. These findings have important implications for exercise behavior in adolescents by maintaining sound communication between family members and developing a healthy lifestyle or value cognition.