title: Inhibition of PGC-1α after chemotherapy-mediated insult confines multiple myeloma cell survival by affecting ROS accumulation.
abstract: 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.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Dedong
authors.initials: D
authors.lastname: Cao
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011719:Pyrazines / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001897:Boronic Acids; D000069286:Bortezomib; D002374:Catalase; D003907:Dexamethasone; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011719:Pyrazines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C486497:PPARGC1A protein, human