PT  - JOURNAL ARTICLE
AU  - NAOTO HORI
AU  - HIROSHI TAZAWA
AU  - YUNCHENG LI
AU  - TOMOHIRO OKURA
AU  - SATORU KIKUCHI
AU  - SHINJI KURODA
AU  - TOSHIAKI OHARA
AU  - KAZUHIRO NOMA
AU  - MASAHIKO NISHIZAKI
AU  - YASUO URATA
AU  - SHUNSUKE KAGAWA
AU  - TOSHIYOSHI FUJIWARA
TI  - Intraperitoneal Administration of p53-armed Oncolytic Adenovirus Inhibits Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells
AID  - 10.21873/anticanres.16678
DP  - 2023 Nov 01
TA  - Anticancer Research
PG  - 4809--4821
VI  - 43
IP  - 11
4099  - http://ar.iiarjournals.org/content/43/11/4809.short
4100  - http://ar.iiarjournals.org/content/43/11/4809.full
SO  - Anticancer Res2023 Nov 01; 43
AB  - 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.