ZHX2 inhibits proliferation and promotes apoptosis of human lung cancer cells through targeting p38MAPK pathway

Cancer Biomark. 2020;27(1):75-84. doi: 10.3233/CBM-190514.

Abstract

Objective: To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis.

Materials and methods: The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot.

Results: The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05).

Conclusion: ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.

Keywords: Lung cancer; Zinc-fingers and homeoboxes 2; apoptosis; migration; proliferation.

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Homeodomain Proteins / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MAP Kinase Signaling System / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Transcription Factors / genetics*
  • p38 Mitogen-Activated Protein Kinases / genetics*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • ZHX2 protein, human
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9