Previous studies have showed promising but short-lived activity of sorafenib in osteosarcoma treatments. Researches have suggested ameliorated sensitivity to standard dose of conventional cancer therapies in combination with histone deacetylase inhibitors (HDACis) through various mechanisms. Herein, for the first time, we exploited the synergism of combination therapies with sorafenib and chidamide, a member of HDACis, in the control of OS using human OS cell lines and OS xenograft mouse model and discussed interactive mechanisms between the two drugs. The combination therapy exerted a strong synergism in the inhibition of OS cell proliferation, meanwhile prominently induced cell apoptosis and cell cycle arrest in G0/G1 phase in OS cells with increased expression of MCL-1, decreased expression of caspase-3 and P21, along with diminished level of the overlapped protein P-ERK1/2. Furthermore, oral administration of the combined treatment led to a more optical therapeutic outcome, including lower degrees of tumoral cell proliferation, greater extent of apoptosis, along with induction of cell cycle arrest in tumor tissues, while exhibiting minimal toxicity. This study shows that the combination of sorafenib and chidamide can combat OS in a synergistic fashion and prompts the promising development of innovative combined therapeutic strategies for OS.
Keywords: Chidamide; Combination therapy; HDACis; Osteosarcoma; Sorafenib; Synergistic anti-tumor activity.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.