Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression.
BACKGROUND
Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor and antiangiogenic activity. We sought to determine pharmacodynamic change in tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib.


METHODS
Tumor biopsies were obtained before and after treatment with celecoxib 400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor angiogenesis and cell proliferation were assessed by immunohistochemistry and gene expression by microarray analysis. Plasma celecoxib concentrations were obtained on days 8 and 14.


RESULTS
Paired samples were analyzed in 15 patients. Microvessel density was reduced in post-treatment samples and mean celecoxib levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up-regulated) were differentially expressed on microarray analysis (p < 0.001). Down-regulated genes included cell cycle regulation-related (cyclin-dependent kinase 2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and presentation-related gene HLA-DM B was up-regulated.


CONCLUSIONS
Celecoxib reduced angiogenesis and induced tumor transcriptional changes. Further characterization of these transcriptional changes in vivo is needed to provide further insights into the effects of celecoxib in neoplastic tissue. Our findings provide a rationale for clinical studies aimed at assessing the efficacy of celecoxib in the treatment of NPC.
Soo
R A
RA
Department of Haematology-Oncology, National University Hospital, Singapore. Ross_SOO@nuh.com.sg
Wu
J
J
Aggarwal
A
A
Tao
Q
Q
Hsieh
W
W
Putti
T
T
Tan
K B
KB
Low
J S W
JS
Soon
W L
WL
Lai
Y F
YF
Mow
B
B
Hsu
S
S
Loh
K S
KS
Tan
L
L
Tan
P
P
Goh
B-C
BC
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011720:Pyrazoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib