In vivo and in vitro inhibition of human gastric cancer progress by upregulating Kank1 gene

Oncol Rep. 2017 Sep;38(3):1663-1669. doi: 10.3892/or.2017.5823. Epub 2017 Jul 17.

Abstract

Recent research has found that Kank1 gene, as one of the important members of the Kank gene family, plays an important role in the occurrence and development of malignant tumors. As a brand new cancer suppressor gene, its expression is significantly downregulated or missing in various kinds of malignant tumors. However, no report on the specific role of Kank1 in the genesis and development of gastric cancer is available yet. In the present study, we found significantly lower expression of Kank1 gene in human gastric cancer cells. When Kank1 gene was upregulated, it was found that the proliferation of gastric cancer cells was obviously inhibited, cell apoptosis occurred and caspase family expression changed with mainly activation of caspase-3 and caspase-9 as well as the apparent imbalance in Bcl-2/Bax ratio. we also found that upregulating Kank1 gene may result in the inhibition of the ability of the invasion and metastasis of tumor cells and the significant change in the expression level of MMP-7 of MMP family, which were confirmed by the in vivo nude mouse experiment, as upregulating Kank1 gene expression may result in decline in the nude mouse tumor formation rate and the significant reduction in the transplanted tumor size. The results above indicate that upregulating the Kank1 gene can inhibit the progress of gastric cancer in vivo and in vitro and its mechanism is closely relevant to apoptosis and the tumor invasion and metastasis.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Caspase 9 / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Matrix Metalloproteinase 7 / genetics
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Stomach Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Up-Regulation / genetics*
  • bcl-2-Associated X Protein / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • KANK1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Caspase 3
  • Caspase 9
  • Matrix Metalloproteinase 7