Intravenous administration of dehydroxymethylepoxyquinomicin with polymer enhances the inhibition of pancreatic carcinoma growth in mice

Hiroto Fujisaki, Yutaka Nakano, Sachiko Matsuda, Keiichi Suzuki, Osamu Itano, Masayuki Tanaka, Shutaro Hori, Yasushi Hasegawa, Yuta Abe, Hiroshi Yagi, Minoru Kitago, Tomohiro Konno, Kazuhiko Ishihara, Keiko Ohno, Satoshi Kishino, Kazuo Umezawa, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background/Aim: Pancreatic cancer, which exhibits resistance to cytotoxic and molecular targeted drugs, has an extremely poor prognosis. Nuclear factor-ĸB (NF-ĸB) is constitutively activated in many pancreatic cancer cases. Although the NF-ĸB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has exhibited anti-cancer effects in pancreatic cancer models, its poor solubility limits its use to intraperitoneal administration. Materials and Methods: Poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) forms stable polymer aggregates with DHMEQ. The stability of DHMEQ aggregated with PMB in the human blood was measured by high-performance liquid chromatography–mass spectrometry (HPLC-MS) ex vivo. Anti-pancreatic cancer effects in AsPC-1 and MIA PaCa-2 pancreatic cancer cells were evaluated by cell growth inhibition assay in vitro and tumor growth inhibition assay in vivo. Results: DHMEQ aggregated with PMB (PMBDHMEQ) remained detectable after 60 min of incubation in the human blood, whereas DHMEQ aggregated with carboxymethyl cellulose (CMC-DHMEQ) was barely detectable. PMB-DHMEQ significantly inhibited AsPC-1 and MIA PaCa-2 cell growth in vitro compared to CMC-DHMEQ. Intravenous administration of PMB-DHMEQ reduced the tumor volume and liver metastasis compared to untreated or CMC-DHMEQ-treated mice. Conclusion: Aggregation with PMB improved the solubility of DHMEQ, and effectively inhibited pancreatic cancer cell growth both in vitro and in vivo.

Original languageEnglish
Pages (from-to)6003-6012
Number of pages10
JournalAnticancer research
Volume41
Issue number12
DOIs
Publication statusPublished - 2021 Dec

Keywords

  • Amphiphilic phospholipid polymer
  • Anti-cancer effects
  • Dehydroxymethylepoxyquinomicin
  • Drug delivery system
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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