Targeting the Wnt signaling pathway with dishevelled and cisplatin synergistically suppresses mesothelioma cell growth.
BACKGROUND
We have previously found that Wnt signaling is activated in mesothelioma cells. To clarify the effect of blocking Wnt signaling in mesothelioma, the expression of dishevelled (Dvl), an intermediator of Wnt signaling, was down-regulated by a reformed type of small interfering RNA (siRNA), stealth RNAi, which can reduce the cytotoxic interferon response unlike conventional siRNA.


METHODS
Mesothelioma cell lines were transfected with stealth RNAi of Dvl, and cell growth and colony formation were examined. The synergistic effect on cell growth of Dvl stealth RNAi and cisplatin in combination was evaluated.


RESULTS
Dvl stealth RNAi down-regulated the expression of Dvl-3 in mesothelioma cells and induced cell cycle aberration which caused suppression of cell growth. Colony formation was also suppressed. Dvl stealth RNAi and cisplatin in combination suppressed cell growth synergistically.


CONCLUSIONS
Our data suggest that inhibition of Wnt signaling leads to significant antitumor effects.
Uematsu
Kazutsugu
K
Division of Clinical Oncology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan. kuematsu@saitama-med.ac.jp
Seki
Nobuhiko
N
Seto
Takashi
T
Isoe
Chie
C
Tsukamoto
Hideo
H
Mikami
Iwao
I
You
Liang
L
He
Biao
B
Xu
Zhidong
Z
Jablons
David M
DM
Eguchi
Kenji
K
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D048708:Cell Growth Processes; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D000072261:Dishevelled Proteins; D015536:Down-Regulation; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D002945:Cisplatin