| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-09-30 |
| タイトル |
|
|
タイトル |
Azithromycin induces read-through of the nonsense Apc allele and prevents intestinal tumorigenesis in C3B6F1 ApcMin/+ mice |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
Semba Ryoko
Morioka Takamitsu
Yanagihara Hiromi
Suzuki Kenshi
Tachibana Hirotaka
Hamoya Takahiro
Horimoto Yoshiya
Imaoka Tatsuhiko
Saito Mitsue
Kakinuma Shizuko
Arai Masami
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Therapeutic strategies that promote read-through of a mutant gene have proved effective for certain non- neoplastic diseases. However, the efficacy of this approach is unproven regarding neoplastic diseases with germline nonsense mutations, including familial adenomatous polyposis. Here we examined the cancer- preventive efficacy of the macrolide antibiotic azithromycin, with a reported read-through effect, on intestinal tumorigenesis in C3B6F1 ApcMin/+mice harboring a nonsense Apc mutation resulting in a truncated Apc protein. Mice were given drinking water lacking azithromycin or containing 0.0125?0.2 mg/mL azithromycin from 3 weeks of age. The small intestine and cecum were analyzed for pathological changes and alterations of intestinal flora. Azithromycin suppressed the number of tumors and the proportion of adenocarcinomas, with the most effective drinking-water concentration being 0.0125 mg/mL. Furthermore, azithromycin recovered the cellular level of full-length Apc, resulting in downregulation of β-catenin and cyclin D1. Conversely, the effect of azithromycin on the diversity of the intestinal microbiota depended on the drinking-water concentration. These results suggest that the balance between azithromycin-mediate read-through of mutant Apc mRNA and antibacterial effects influences intestinal tumorigenesis. Thus, azithromycin is a potential anticancer agent for familial adenomatous polyposis patients harboring nonsense mutations. |
| 書誌情報 |
Biomedicine & Pharmacotherapy
巻 164,
p. 114968,
発行日 2023-06
|
| 出版者 |
|
|
出版者 |
Elsevier |
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1950-6007 |
| DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1016/j.biopha.2023.114968 |
