RESUMEN
NVS-ZP7-4 was identified as a novel chemical reagent targeting the zinc input protein ZIP7, which accounts for the zinc surge from the apparatus to the cytoplasm. Since zinc dysregulation is related to multiple diseases, in this study, we aimed to identify the anti-tumor effects of NVS-ZP7-4 and explore the molecular mechanisms of NVS-ZP7-4 in hepatocellular carcinoma (HCC) progression. We found that NVS-ZP7-4 inhibited cell viability, caused cell cycle arrest, induced apoptosis, and inhibited the proliferation, migration, and invasion of HCCLM3 and Huh7 cells. We further investigated the inhibited activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was involved in the antitumor effect of NVS-ZP7-4 in HCC. Furthermore, NVS-ZP7-4 inhibited HCC tumor growth in vivo. The present study demonstrated that NVS-ZP7-4 is a promising therapeutic target for HCC by regulating PI3K/AKT signaling.
Asunto(s)
Carcinoma Hepatocelular , Proteínas de Transporte de Catión , Neoplasias Hepáticas , Humanos , Apoptosis , Carcinogénesis/genética , Carcinoma Hepatocelular/genética , Transformación Celular Neoplásica , Retículo Endoplásmico , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , ZincRESUMEN
Desmogleins (DSGs), with the ability to link adjacent cells, have been shown to participate in the development of malignancy. DSG3 was up-regulated in various cancers, including lung, head and neck, and esophagus squamous cell carcinoma, which contributed to the tumor progression. The role of DSG3 in pancreatic ductal adenocarcinoma (PDAC) still remains elusive. Here, the expression of DSG3 was found to be enhanced in pancreatic cancer cell lines in vitro. Functional assays showed that shRNA-mediated knockdown of DSG3 decreased cell viability of pancreatic cancer cells and retarded the cell proliferation, migration and invasion. However, pcDNA-mediated over-expression of DSG3 exhibited reversed effect on pancreatic cancer cell progression. In addition, the in vivo assay demonstrated that transfection of shDSG3 lentiviruses into pancreatic cancer cells repressed the tumorigenicity of PDAC after the cancer cells were transplanted into mice subcutaneously. Elevated DSG3 expression promoted the phosphorylation of Src (p-Src), focal adhesion kinase (p-FAK) and AKT (p-AKT) in vitro, while silence of DSG3 reduced the expression of p-Src, p-FAK and p-AKT both in vitro and in vivo. In conclusion, DSG3, as an oncogene, contributed to the tumorigenicity of PDAC through activating Src-FAK signaling.