title: Combination of AZD2281 (Olaparib) and GX15-070 (Obatoclax) results in synergistic antitumor activities in preclinical models of pancreatic cancer.
abstract: In this study, we explored the antitumor activities of the PARP inhibitor AZD2281 (Olaparib) and the pan-Bcl-2 inhibitor GX15-070 (Obatoclax) in six pancreatic cancer cell lines. While both agents were able to cause growth arrest and limited apoptosis, the combination of the two was able to synergistically cause growth arrest and non-apoptotic cell death. Furthermore, in an in vivo xenograft model, the combination caused substantially increased tumor necrosis compared to either treatment alone. Our results support further investigation of the combination of Bcl-2 and PARP inhibitors for the treatment of pancreatic cancer.
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Niu
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Pathophysiology College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Hebin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology College of Basic Medical Sciences, Jilin University, Changchun, China. Electronic address: zhao_lj@jlu.edu.cn.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The State Engineering Laboratory of AIDS Vaccine, College of Life Sciences, Jilin University, Changchun, China; Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: gey@karmanos.org.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ge
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007211:Indoles; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010793:Phthalazines / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004791:Enzyme Inhibitors; D007211:Indoles; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D011065:Poly(ADP-ribose) Polymerases; C520962:obatoclax; C531550:olaparib
keywords: Drug combination; Obatoclax; Olaparib; Pancreatic cancer