Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer

Wataru Ishikawa, Satoru Kikuchi, Toshihiro Ogawa, Motoyasu Tabuchi, Hiroshi Tazawa, Shinji Kuroda, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Yasuo Urata, Toshiyoshi Fujiwara

Research output: Contribution to journalArticlepeer-review

Abstract

Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer. Paclitaxel (PTX) enhanced the replication of telomerase-specific oncolytic adenovirus in cancer cells and the penetration of the virus into the disseminated nodules of gastric cancer (GC) in the abdominal cavity. The intraperitoneal virotherapy combined with PTX may be a novel promising therapy for peritoneal metastasis of GC.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume18
DOIs
Publication statusPublished - Sep 25 2020

Keywords

  • adenovirus
  • gastric cancer
  • intraperitoneal chemotherapy
  • oncolytic virus
  • paclitaxel
  • peritoneal metastasis

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer'. Together they form a unique fingerprint.

Cite this