Surgically induced accelerated local and distant tumor growth is significantly attenuated by selective COX-2 inhibition.
BACKGROUND
Even after apparently curative resection, lung cancer recurrence continues to lead to high mortality levels. The aim of this study was to assess the effects of cyclooxygenase-2 (COX-2) inhibitor on local and systemic recurrent tumor growth.


METHODS
C57BL/6 mice underwent mammary fat pad inoculation with 3LL cells. After two weeks growth, flank tumors were resected completely and followed for recurrent tumor growth. Postresection mice were randomized to receive placebo alone (group 1) or the selective COX-2 inhibitor, rofecoxib (group 2), daily for two weeks by tube feeding. Recurrent tumor growth kinetics were compared for both groups. Two weeks following primary tumor excision animals were sacrificed, after which lungs were resected and pulmonary metastatic burden was assessed using the lung-body weight ratio. Apoptotic and mitotic indices were established for recurrent tumors and lungs, using hematoxylin and eosin histology.


RESULTS
Two weeks postexcision of the primary tumor, recurrent tumors in the placebo group were significantly greater than the treatment group (p = 0.002). While primary tumors were typically encapsulated and not adherent, recurrent tumors in the placebo group were invasive, adherent to the chest wall and the overlying wound. In contrast, recurrent tumors in the treatment group were nonadherent to the chest wall. Moreover, postoperative pulmonary metastatic burden was significantly reduced in treated animals. Histologic examination revealed increased apoptosis as well as an increase in the apoptosis-mitosis ratio in treated animals.


CONCLUSIONS
Primary tumor excision was associated with accelerated local and systemic tumor recurrence. However, these effects were significantly attenuated using selective COX-2 inhibition. The COX-2-inhibition was associated with increased levels of apoptosis. These findings endorse a role for COX-2 inhibition in the secondary prevention of lung cancer recurrence at both local and systemic levels.
Qadri
Syed S A
SS
Cork University Hospital, Wilton, Cork, Republic of Ireland.
Wang
Jiang-Huai
JH
Coffey
John Calvin
JC
Alam
Mahmood
M
O'Donnell
Aonghus
A
Aherne
Thomas
T
Redmond
Henry P
HP
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D007783:Lactones / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D013450:Sulfones / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib