Expression of bcl-2 correlates with poor prognosis and modulates migration of nasopharyngeal carcinoma cells

Clin Chim Acta. 2010 Mar;411(5-6):400-5. doi: 10.1016/j.cca.2009.12.010. Epub 2009 Dec 28.

Abstract

Background: The role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC).

Methods: From 1996 to 2000, 145 patients with newly diagnosed NPC who were treated with high dose radiotherapy were enrolled. The relationship between bcl-2 expression, TNM stage, and disease-specific survival was analyzed. Furthermore, the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and cell metastasis.

Results: Among the 145 patients, 47 (32.4%) of them were bcl-2 positive. The expression of bcl-2 was significantly correlated with neck lymph node metastasis (p=0.006), and patients with negative bcl-2 expression had better disease-free survival (p=0.007). A Cox regression model revealed that only bcl-2 expression (p=0.023) and stage IV (p=0.043) were statistically significant in the prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2 inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP-2 in HONE-1 cells.

Conclusions: Bcl-2 expression represents an important and easily assayed prognostic factor, and it may play an important role in lymph node metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature for the prevention of cancer metastasis.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzopyrans / pharmacology
  • Cell Movement*
  • Disease-Free Survival
  • Dose-Response Relationship, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Middle Aged
  • Nasopharyngeal Neoplasms / diagnosis*
  • Nasopharyngeal Neoplasms / pathology*
  • Nasopharyngeal Neoplasms / therapy
  • Neoplasm Staging
  • Nitriles / pharmacology
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Benzopyrans
  • Matrix Metalloproteinase Inhibitors
  • Nitriles
  • Proto-Oncogene Proteins c-bcl-2
  • ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
  • Matrix Metalloproteinase 2