机构：[1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan[2]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[3]Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan[4]Department of Respirology, GraduateSchool of Medicine, Chiba University, Chiba, Japan[5]Niimi College, Niimi, Japan[6]Department of Thoracic Diseases, Chiba Cancer Center, Chiba, Japan[7]Department ofPathology, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, Japan[8]Department of Surgery, School of Medicine, Toho University, Tokyo, Japan.
We examined the combinatory antitumor effects of adenoviruses expressing human mda-7/IL-24 gene (Ad-mda-7) and chemotherapeutic agents on nine kinds of human esophageal carcinoma cells. All the carcinoma cells expressed the melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) receptor complexes, IL-20R2 and either IL-20R1 or IL-22R1, and were susceptible to Ad-mda-7, whereas fibroblasts were positive only for IL-20R2 gene and resistant to Ad-mda-7-mediated cytotoxicity. Sensitivity of these esophageal carcinoma cells to Ad-mda-7 was however lower than that to Ad expressing the wild-type p53 gene. We thereby investigated a possible combination of Ad-mda-7 and anticancer agents and found that Ad-mda-7 with 5-fluorouracil (5-FU), cisplatin, mitomycin C or etoposide produced greater cytotoxic effects than those by Ad-mda-7 or the agent alone. Halfmaximal inhibitory concentration values of the agents in respective cells were decreased by the combination with Ad-mda-7. Cell cycle analyses showed that Ad-mda-7 and 5-FU increased G2/M-phase and S-phase populations, respectively, and the combination augmented sub-G1 populations. Ad-mda-7-treated cells showed cleavages of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase, but the cleavage levels were not different from those of the combination-treated cells. Ad-mda-7 treatments upregulated Akt phosphorylation but suppressed I kappa B-alpha levels, whereas 5-FU treatments induced phosphorylation of p53 and extracellular signal-regulated protein kinases 1 and 2. Molecular changes caused by the combination were similar to those by Admda-7 treatments, but the Ad-mda-7-mediated upregulation of Akt phosphorylation decreased with the combination. These data collectively suggest that Ad-mda-7 induced apoptosis despite Akt activation and that the combinatory antitumor effects with 5-FU were produced partly by downregulating the Ad-mda-7-induced Akt activation.
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; Grants-in-Aid for Scientific ResearchMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [26462000, 23591951] Funding Source: KAKEN
语种：
外文
被引次数：
WOS：
PubmedID：
中科院分区：
出版当年[2014]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区医学：研究与实验3 区肿瘤学4 区遗传学
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[2014]版：
Q2BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ3ONCOLOGYQ3GENETICS & HEREDITYQ3MEDICINE, RESEARCH & EXPERIMENTAL
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, Chiba, Japan[2]Department of Hematology, The Fourth Hospital of Hebei Medical University,Shijiazhuang, China
通讯作者：
通讯机构：[1]Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan[3]Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, 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)：
Ma G.,Kawamura K.,Shan Y.,et al.Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma[J].CANCER GENE THERAPY.2014,21(1):31-37.doi:10.1038/cgt.2013.79.
APA：
Ma, G.,Kawamura, K.,Shan, Y.,Okamoto, S.,Li, Q....&Tagawa, M..(2014).Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma.CANCER GENE THERAPY,21,(1)
MLA：
Ma, G.,et al."Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma".CANCER GENE THERAPY 21..1(2014):31-37
