Expression of bcl-2 correlates with poor prognosis and modulates migration of nasopharyngeal carcinoma cells.
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.
Chen
Mu-Kuan
MK
Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan. 53780@cch.org.tw
Yang
Shun-Fa
SF
Lai
Jui-Chung
JC
Yeh
Kun-Tu
KT
Yang
Jia-Sin
JS
Chen
Li-Sheng
LS
Chen
Hui-Chuan
HC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology; D002465:Cell Movement; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D009570:Nitriles / Q000494:pharmacology; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D001578:Benzopyrans; D061965:Matrix Metalloproteinase Inhibitors; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D020778:Matrix Metalloproteinase 2