Heat-shock protein 90 inhibitors synergistically enhance melanoma differentiation-associated gene-7-mediated cell killing of human pancreatic carcinoma
机构：[1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan[2]Department of Gynecology and Obstetrics, The Fourth Hospital of HebeiMedical University, Shijiazhuang, China[3]Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan[4]Department ofThoracic Diseases, Chiba Cancer Center, Chuo-ku, Chiba, Japan[5]Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China临床科室血液内科河北医科大学第四医院[6]Departmentof Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, China[7]Cell Therapy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China[8]Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院[9]Department of General Surgery, The Second Hospital of Hebei MedicalUniversity, Shijiazhuang, China[10]Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China河北医科大学第四医院[11]Department of Endoscopy, The Fourth Hospital ofHebei Medical University, Shijiazhuang, China医技科室内镜科河北医科大学第四医院[12]SVP Translational Medicine, Intrexon Corporation, Germantown, MD, USA.
Pancreatic cancer is one of the intractable diseases and an effective therapeutic strategy is required to improve the prognosis. We examined possible antitumor effects of adenoviruses expressing melanoma differentiation-associated gene-7/interleukin-24 (Admda-7) and a heat-shock protein 90 (Hsp90) inhibitor to human pancreatic carcinoma cells. Ad-mda-7 and an Hsp90 inhibitor, geldanamycin (GA), produced cytotoxic effects, and a combinatory use of Ad-mda-7 and GA further achieved synergistic effects. Administration of N-acetyl-L-cysteine, an inhibitor of reactive oxygen species, eliminated Ad-mda-7- and GA-mediated cytotoxicity. Ad-mda-7 augmented phosphorylated AKT levels but GA did not influence the phosphorylation. GA-treated cells showed cleavage of poly-(ADP-ribose) polymerase but not caspase-3, and upregulated Hsp70 and LC3A/B II levels, whereas Ad-mda-7-treated cells did not. GA treatments augmented ubiquitination and markedly increased melanoma differentiation-associated gene-7 (MDA-7) expression levels. These findings suggest that Ad-mda-7-mediated cytotoxicity is dependent on reactive oxygen species but independent of apoptosis or autophagy, and that GA-mediated cytotoxicity was linked with caspase-independent apoptosis and/or autophagy. A mechanism underlying the combinatory effects of Ad-mda-7 and GA remained complex and the synergism is attributable to multiple factors including increased MDA-7 protein stability by GA.
基金：
Ministry of Education, Culture, Sports, Science and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT); Ministry of Health, Labor and Welfare of JapanMinistry of Health, Labour and Welfare, Japan; Nichias Corporation
语种：
外文
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出版当年[2013]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验4 区肿瘤学
JCR分区：
出版当年[2013]版：
Q2MEDICINE, RESEARCH & EXPERIMENTALQ2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ3GENETICS & HEREDITYQ3ONCOLOGY
最新[2024]版：
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ1ONCOLOGY
第一作者机构：[1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan[2]Department of Gynecology and Obstetrics, The Fourth Hospital of HebeiMedical University, Shijiazhuang, China
通讯作者：
通讯机构：[1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan[3]Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan[*1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
推荐引用方式(GB/T 7714)：
Zhang Z.,Kawamura K.,Jiang Y.,et al.Heat-shock protein 90 inhibitors synergistically enhance melanoma differentiation-associated gene-7-mediated cell killing of human pancreatic carcinoma[J].CANCER GENE THERAPY.2013,20(12):663-670.doi:10.1038/cgt.2013.66.
APA：
Zhang, Z.,Kawamura, K.,Jiang, Y.,Shingyoji, M.,Ma, G....&Tagawa, M..(2013).Heat-shock protein 90 inhibitors synergistically enhance melanoma differentiation-associated gene-7-mediated cell killing of human pancreatic carcinoma.CANCER GENE THERAPY,20,(12)
MLA：
Zhang, Z.,et al."Heat-shock protein 90 inhibitors synergistically enhance melanoma differentiation-associated gene-7-mediated cell killing of human pancreatic carcinoma".CANCER GENE THERAPY 20..12(2013):663-670
