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Therapeutic effects of chidamide on myeloma-associated bone disease
relapse, our data has shown that chidamide overcomes the drug resistance mediated by the interaction between MM cells and the microenvironment. Moreover, the good anti-myeloma effect of chidamide on the disseminated MM mouse model reveals the efficacy of chidamide in the presence of the BM microenvironment.
HDACs regulate a variety of targets involved in differ-
ent cell functions and processes, such as apoptosis, the cell cycle and differentiation.20 Chidamide inhibited HDAC activity and induced cell cycle arrest in G1 phase, accom- panied by cell apoptosis. Notably, cell cycle arrest and the alterations in levels of related proteins were not reversed by the pan-caspase inhibitor. HDAC inhibitors cause cell cycle arrest though several pathways, the most important
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Figure 5. Dual anti-myeloma and bone-protective effects of chidamide on a disseminated myeloma murine model. (A) Chidamide suppresses the growth of MM xenografts, ***P<0.001. (B) Tumor volumes, serum human Igλ levels in each group and in vivo bioluminescence imaging were used to compare the tumor burdens between the two groups. (C) Serum levels of CTX-I (**P<0.01) and PINP (***P<0.001) in each group. (D) Micro-CT three-dimensional reconstructed images from the vehicle and chidamide groups. (E) Micro-CT parameters of the bone in the vehicle and chidamide groups. Trabecular numbers, ***P<0.001; trabecular space, **P<0.01; BV/TV, non-significant (ns).
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