論文 - 詳細
| RRC ID | 77189 |
|---|---|
| 著者 | Hori N, Tazawa H, Li Y, Okura T, Kikuchi S, Kuroda S, Ohara T, Noma K, Nishizaki M, Urata Y, Kagawa S, Fujiwara T. |
| タイトル | Intraperitoneal Administration of p53-armed Oncolytic Adenovirus Inhibits Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to poor prognosis. However, efforts to develop antitumor strategies for preventing the peritoneal metastasis of GC have been unsuccessful. As diffuse-type GC cells often carry a genetic alteration in the tumor suppressor p53 gene, p53 restoration may be a potent strategy for preventing peritoneal metastasis of GC. In this study, we investigated the therapeutic potential of p53-expressing adenoviral vectors against peritoneal metastasis of diffuse-type GC cells. MATERIALS AND METHODS:Three diffuse-type human GC cell types with different p53 statuses (p53-wild type NUGC-4, p53-mutant type GCIY, and p53-null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by the p53-expressing, replication-deficient adenovirus Ad-p53 and oncolytic adenovirus OBP-702. Viability, apoptosis, and autophagy of virus-treated GC cells were analyzed under normal and sphere-forming culture conditions using the XTT assay and western blot analysis. The in vivo antitumor effects of OBP-702 and Ad-p53 were assessed using xenograft tumor models involving peritoneal metastasis of NUGC-4 and GCIY cells. RESULTS:Under normal and sphere-forming culture conditions, OBP-702 induced a significantly greater antitumor effect in GC cells compared with Ad-p53 by strongly inducing p53-mediated apoptosis and autophagy and receptor tyrosine kinase suppression. In vivo experiments demonstrated that intraperitoneal administration of OBP-702 significantly suppressed the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, leading to prolonged survival of mice. CONCLUSION:Intraperitoneal administration of OBP-702 inhibits the peritoneal metastasis of GC cells by inducing p53-mediated cytopathic activity. |
| 巻・号 | 43(11) |
| ページ | 4809-4821 |
| 公開日 | 2023-11-1 |
| DOI | 10.21873/anticanres.16678 |
| PII | 43/11/4809 |
| PMID | 37909979 |
| MeSH | Adenoviridae / genetics Animals Disease Models, Animal Humans Mice Peritoneal Neoplasms* / prevention & control Peritoneum Stomach Neoplasms* / therapy Tumor Suppressor Protein p53 / genetics |
| IF | 1.994 |
| リソース情報 | |
| ヒト・動物細胞 | GCIY(RCB0555) Kato III(RCB2088) |