Abstract

BackgroundGastric cancer (GC) is a global health problem because of limited treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its effects on GC remains largely unknown. Notch signaling plays a critical role in cell proliferation, differentiation and apoptosis. Therefore, it may contribute to the development of GC. This study aims to explore the role of Notch2 in ACGs’ activities in GC cells.ResultsACGs inhibited GC cells’ viability in a dose dependent manner and led to cell apoptosis and cell cycle arrest in G0/G1 phase with an increased Notch2 expression. Additionally, Notch2 siRNA reduced ACGs-induced cell growth inhibition while Notch2 cDNA transfection did the opposite.Materials and MethodsACGs were administrated in GC cells and cell proliferation was assayed by MTS, cell apoptosis and cell cycle were detected by flow cytometry. Additionally, the expression of Notch2 and the downstream target Hes1 were identified by Western blot. Furthermore, Notch2-siRNA transfection and Notch2-cDNA were performed to investigate the role of Notch2 in the antitumor effect of ACGs. Conclusions: Up-regulation of Notch2 by ACGs is a potential therapeutic strategy for GC.

Highlights

  • Gastric cancer (GC) is one of the most common malignancies in global scale

  • In order to evaluate the possible role of Notch2 in gastric carcinogenesis, we screened a panel of 5 GC cell lines for the relative expression of Notch2 at mRNA level by quantitative real-time PCR and at protein level by western blot

  • Notch2 expression was higher in AGS and SGC-7901 and lower in MGC803, MKN-28 and MKN-45 (Figure 1A), which was consistent with the published results

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Summary

Introduction

Gastric cancer (GC) is one of the most common malignancies in global scale. It acts as one of major causes of cancer-related death. Many current available treatments for gastric cancer, such as surgery and chemotherapy, are less optimal, and the prognosis of GC is rather poor. This is because of lacking complete understanding in the mechanisms for GC. It is critical to explore alternative treatments and develop more effective therapies. Gastric cancer (GC) is a global health problem because of limited treatments and poor prognosis. This study aims to explore the role of Notch in ACGs’ activities in GC cells

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