Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway.

摘要

BACKGROUND: Chondrosarcoma represents the second most common primary malignant bone tumor causing significant morbidity due to local recurrence and limited treatment options. Conventional cytotoxic chemotherapy has been proven to be largely ineffective to this sarcoma. Here we report that sorafenib is effective in growth inhibition of chondrosarcoma cell lines in vitro. METHODS: Chondrosarcoma cell lines (SW1353 and CRL7891) were treated with sorafenib. Flow cytometry, DAPI assay, and Western blotting were employed to determine the effects of sorafenib in inhibitory proliferation and induce apoptosis in chondrosarcoma cells in vitro. RESULTS: The results showed that sorafenib effectively inhibited cell growth and induced apoptosis in chondrosarcoma cells, which was concurrent with inhibition of the expression of phospho-MEK and phospho-ERK. Further more the expression levels of cyclin D1, Rb and anti-apoptotic proteins Bcl-xl and Mcl-1 significantly reduced, but no changes in Bcl-2 and Bax. We although detected the expression of Akt, JNK, p38 and their respective phosphoprotein, but did not found meaningful changes. CONCLUSIONS: Our findings demonstrate that sorafenib inhibited the Ras/Raf/MAPK pathway in a time- and dose-dependent fashion in chondrosarcoma cell lines SW1353 and CRL7891 and suggest that sorafenib may be a new therapeutic option for patients with chondrosarcoma.