Selective Cox-2 inhibition attenuates recurrent tumor growth

Abstract

Introduction: High recurrence of lung cancer is a major problem despite complete successful resection of lung cancer and adjuvant therapies. Method: C57/BL6 mice (10/group) underwent mammary fat pad inoculation with 3LL cells (5 x 105/animal). After 2-weeks, flank tumours were resected completely. Thereafter mice were randomised to receive placebo alone (Group-1) or COX-2-inhibitor (Group-2), daily for two weeks by gavage (40 mg/kg). Lungs were resected at sacrifice and pulmonary metastatic burden was assessed using lung/body weight ratio. Apoptotic and mitotic indices were established for recurrent tumours and lungs, using H&E histology. Result: There were no statistical differences in flank tumour volume between groups, at the time of excision (1.53 ± 0.29 cm vs. 1.36 ± 0.44 cm). Two weeks post-excision of primary tumor, tumours in the placebo-treated group were significantly greater in volume compared with those of the treatment group (2.65 ± 0.74 cm vs. 1.22 ± 0.8 cm (p < 0.001)). Whilst primary tumours were typically capsulated and not adherent, recurrent tumours in Group-1 were invasive, adherent to the chest wall and overlying wound. In contrast, recurrent tumours in Group-2 animals were non-adherent to chest wall. Moreover, postoperative pulmonary metastatic burden was significantly reduced in treated animals. Histological examination revealed increased apoptosis as well as an increase in the apoptosis/mitosis ratio in treatment group [0.83 vs. 0.68]. Conclusion: Cytoreductive surgery for cancer was associated with accelerated recurrent tumor growth and its metastasis. However, these effects were significantly attenuated using selective COX-2 inhibition. 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 the local and systemic level.