Inhibition of PGC-1α after chemotherapy-mediated insult confines multiple myeloma cell survival by affecting ROS accumulation.

Peroxisome proliferator‑activated receptor-γ coactivator-1α (PGC-1α) is a key regulator of reactive oxygen species (ROS). However, whether it has the same role in multiple myeloma (MM), especially after treatement with chemotherapy, remains unclear. After treating cells with bortezomib or dexamethasone, the expression of PGC-1α, superoxide dismutase 2 (SOD-2) and catalase (CAT) was examined by RT-PCR. PGC-1α expression was also analyzed by western blotting. Small‑interference RNA (siRNA) was applied to inhibit the expression of PGC-1α after chemotherapy. Changes of cellular ROS and apoptosis were detected by flow cytometric analysis. Cell proliferation was assessed by MTT assay. The expression of PGC-1α and SOD-2 following chemotherapy were upregulated, but accompanied by increased ROS. Following suppression of PGC-1α, ROS levels, as well as the pro-apoptotic effect of bortezomib were further increased. These findings suggested that PGC-1α regulates ROS in MM, and that inhibition of elevated PGC-1α following stimulation by chemotherapy leads to a higher level of ROS by downregulating antioxidant factors, eventually enhancing the antitumor effect of bortezomib.