A small interfering RNA targeting proteinase-activated receptor-2 is effective in suppression of tumor growth in a Panc1 xenograft model.
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.
Iwaki
Kentaro
K
Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan. iwaki@ med.oita-u.ac.jp
Shibata
Kohei
K
Ohta
Masayuki
M
Endo
Yuichi
Y
Uchida
Hiroki
H
Tominaga
Masayuki
M
Okunaga
Ryoki
R
Kai
Seiichiro
S
Kitano
Seigo
S
D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D010957:Plasmids; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044464:Receptor, PAR-2