A small interfering RNA targeting proteinase-activated receptor-2 is effective in suppression of tumor growth in a Panc1 xenograft model

Kentaro Iwaki, Kohei Shibata, Masayuki Ohta, Yuichi Endo, Hiroki Uchida, Masayuki Tominaga, Ryoki Okunaga, Seiichiro Kai, Seigo Kitano

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Proteinase-activated receptor-2 (PAR-2), which is a G protein-coupled receptor, is activated in inflammatory processes and cell proliferation. We previously demonstrated that an anti-PAR-2 antibody suppresses proliferation of human pancreatic cells in vitro. However, there have been no studies of PAR-2 signaling pathways in vivo. The aim of this study was to determine whether blockade of PAR-2 by RNA interference influences pancreatic tumor growth. We originally constructed small interfering RNAs (siRNAs) targeting human PAR-2, and performed cell proliferation assays of Panc1 human pancreatic cancer cell line with these siRNAs. Intratumoral treatment with these PAR-2 siRNAs and atelocollagen was also performed in a xenograft model with nude mice and Panc1 cells. siRNAs against human PAR-2 inhibited proliferation of Panc1 cells, whereas control scramble siRNAs had no effect on proliferation. The PAR-2 siRNAs dramatically suppressed tumor growth in the xenograft model. PAR-2-specific siRNA inhibited growth of human pancreatic cancer cells both in vitro and in vivo. Blockade of PAR-2 signaling by siRNA may be a novel strategy to treat pancreatic cancer.

Original languageEnglish
Pages (from-to)658-663
Number of pages6
JournalInternational Journal of Cancer
Volume122
Issue number3
DOIs
Publication statusPublished - Feb 1 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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