IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin β3-Mediated NF-κB Signaling

Interferon. (IFN-gamma), a multifunctional cytokine, was upregulated in the resected gastric cancer tissue. However, whether IFN-gamma is involved in the regulation of gastric cancer has not been well elucidated. Herein, we aimed to investigate the effects and mechanism of IFN-gamma on gastric cancer. In this study, we found a vital role of IFN-gamma in enhancing proliferation, inhibiting apoptosis, and promoting cell migration and invasion in gastric cancer cells SGC-7901 and MGC-803. Additionally, IFN-gamma activated nuclear factor kappa B (NF-kappa B) signaling pathway by upregulating the phosphorylation expression of p65 and I kappa B alpha, and induced the expression of integrin beta 3 in vitro. Therefore, to further investigate the relationship between IFN-gamma and integrin beta 3, SGC-7901 cells were transfected with integrin beta 3 siRNA. And then cells expressed lower cell viability, migration, and invasion rates, while cell apoptosis was significantly enhanced. Meanwhile, expression of integrin beta 3, MMP-2, MMP-9, and NF-kappa B, including p65 and I kappa Ba, and the nuclear translocation of NF-kappa B/p65 were dramatically repressed, whereas IFN-gamma significantly improved the effects. Moreover, in vivo, the experiment of xenograft model and pulmonary metastasis model also retarded in integrin beta 3 siRNA group. And the expression of integrin beta 3, MMP-2, MMP-9, and NF-kappa B was repressed. However, the treatment with IFN-gamma improved tumor volume, lung/total weight, tumor nodules, and the protein expression described above compared with integrin beta 3 siRNA group. Overall, the results indicated that IFN-gamma induces gastric cancer cell proliferation and metastasis partially through the upregulation of integrin beta 3-mediated NF-kappa B signaling. Hence, the inhibition of IFN-gamma or integrin beta 3 may be the key for the treatment of gastric cancer.