Involvement of human beta-defensin-2 in proliferation of transformed cells of human cervix

Exp Oncol. 2005 Dec;27(4):308-13.

Abstract

Aim: To evaluate the influence of human beta-defensin-2 (hBD-2) on viability and proliferation of cultured human epithelial cells and the patterns of hBD-2 expression in normal tissues and early-stage human cervical neoplasia in the relation to proliferative state of these cells.

Materials and methods: The influence of recombinant hBD-2 on viability and proliferation of cultured cells of A431 and M-HeLa lines in vitro was performed by MTT-test, 3H-thymidine incorporation and cell counting techniques. Immunohistochemical analysis of expression of hBD-2 and PCNA in tissue samples (10 normal cases (control), 30 carcinomas of the cervix uteri: 15 - squamous cell carcinoma in situ (Stage 0), and 15 squamous cell carcinoma (Stage Ia)) was performed with the use of anti-hBD-2 and anti-PCNA-mAbs, respectively.

Results: We have revealed that hBD-2 significantly stimulated proliferation of A431 and M-HeLa cells in a concentration-dependent manner in the range of 0.1-2 microg/ml, whilst at higher concentrations (> 3-5 microg/ml) it negatively influenced cell viability. The results of immunohistochemical study have shown that malignant transformation of human cervical epithelium is accompanied by the increase of expression of hBD-2 and PCNA. However, the correlative analysis of the expression of the mentioned markers has revealed no relation between them.

Conclusion: The effect of hBD-2 on viability and proliferation of cultured epithelial cells possesses a concentration-dependent character. Expression of hBD-2 is increased in early-stage cervical carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects*
  • Cell Transformation, Neoplastic / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Proliferating Cell Nuclear Antigen / biosynthesis
  • Proliferating Cell Nuclear Antigen / drug effects
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Uterine Cervical Neoplasms / metabolism*
  • beta-Defensins / metabolism*
  • beta-Defensins / pharmacology

Substances

  • DEFB4A protein, human
  • Proliferating Cell Nuclear Antigen
  • Recombinant Proteins
  • beta-Defensins