Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

Area of Science:

• Oncology
• Pharmacology

Background:

• Drug resistance is a primary driver of relapse and mortality in multiple myeloma (MM).
• There is a critical need for novel therapeutic strategies to overcome drug resistance in MM.

Purpose of the Study:

• To evaluate the anti-tumor efficacy of Chidamide (CHI) in multiple myeloma (MM).
• To investigate the synergistic effect of combining CHI with Bortezomib (BTZ) in MM treatment.

Main Methods:

• In vitro and in vivo studies were conducted using MM cell lines and models.
• Chidamide (CHI) and Bortezomib (BTZ) were administered individually and in combination.
• Mechanistic studies assessed reactive oxygen species (ROS) production, DNA damage, apoptosis, and cell cycle progression.

Main Results:

• Chidamide (CHI) demonstrated significant anti-tumor activity in MM cells, correlated with HDAC1 expression.
• Combination therapy with CHI and BTZ exhibited synergistic effects, inducing apoptosis and G0/G1 cell cycle arrest.
• The synergistic effect was linked to increased ROS-dependent DNA damage and modulation of apoptosis and cell cycle pathways.

Conclusions:

• Chidamide (CHI) possesses potent anti-myeloma activity and can sensitize MM cells to Bortezomib (BTZ).
• The combination of CHI and BTZ offers a promising therapeutic approach for managing drug-resistant multiple myeloma.