Abstract
In both Enchondromatosis (EC) and Multiple Osteochondromas (MO), multiple benign cartilaginous tumours occur, which have a severely increased risk of malignant progression. Preventing new tumor formation and malignant progression would benefit the prognosis of these patients. A protective effect of selective Cox-2 inhibitor celecoxib, has been suggested against development and growth of colorectal cancer in familial syndromes. At last year’s EMSOS meeting we reported on expression of Cox-2 in 37% (central) – 46% (peripheral) of conventional chondrosarcomas. mRNA levels of EC related tumours were slightly higher than the solitary tumours. Celecoxib treatment of the chondrosarcoma cell lines resulted in a 3 fold decrease of PGE2 levels already at 5 μM. A significant decrease in proliferation was found at 10 μM in OUMS27 and at 25 μM in SW1353 and CH2879 compared to DMSO controls.
For the present study we assessed the (prophylactic) effect of celecoxib on chondrosarcoma growth in vivo using a xenograft model of immunoincompetent nude mice which were injected with cell line CH2879 subcutaneously. Tumour volume was measured during 8 weeks. Celecoxib serum levels were determined by HPLC. Expression of proliferation marker Ki-67 and Cox-2 was assessed by IHC.
Our in vivo results also showed a beneficial effect of high dose prophylactic celecoxib treatment. Tumour volumes were negatively correlated with celecoxib serum levels (r2=0.152). However, at the end of pubertal growth of the mice, a catch-up tumour growth was observed, resulting in the absence of differences in tumour volume between control and treatment groups. Accordingly, proliferation marker Ki67 was higher expressed in the treated groups at sacrifice.
This suggests that there is no role for celecoxib in the treatment of adult chondrosarcoma patients. Celecoxib treatment of younger patients, especially to prevent formation of new tumours in EC and OC patients, might be beneficial, however more research is necessary.
Correspondence should be addressed to Professor Stefan Bielack, Olgahospital, Klinikum Stuttgart, Bismarkstrasse 8, D-70176 Stuttgart, Germany. Email: s.bielack@klinikum_stuttgart.de
