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Hyperthermia synergizes with tissue factor knockdown to suppress the growth and hepatic metastasis of colorectal cancer in orthotopic tumor model
Author(s) -
Li Hui,
Tian MaoLin,
Yu Ge,
Liu YuCun,
Wang Xin,
Zhang Jing,
Ji ShiQi,
Zhu Jing,
Wan YuanLian,
Tang JianQiang
Publication year - 2012
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23136
Subject(s) - medicine , colorectal cancer , metastasis , gene knockdown , hyperthermia , cancer research , oncology , cancer , cell culture , biology , genetics
Background Tissue factor (TF) is a significant risk factor for tumor growth and hepatic metastasis in patients with colorectal cancer (CRC). This study aimed to investigate whether hyperthermia has synergistic anti‐tumor effects with TF knockdown in suppressing CRC progression and metastasis in vitro and in vivo. Methods Human colorectal cancer LOVO cells were treated by hyperthermia at 44°C for 2 hr or/and TF siRNA. Then the cells were subjected to colony formation assay. Apoptosis was analyzed by flow cytometry, confocal microscopy, and transmission electron microscopy. The cell migration and invasion abilities were analyzed by wound healing and matrigel assay. In addition, orthotopic nude mice model of CRC was established. Results Hyperthermia synergized with TF knockdown to reduce colony formation ability, induce apoptosis, and suppress the migration and invasion of LOVO cells in vitro. Moreover, hyperthermia in combination with TF depletion inhibited the growth and hepatic metastasis of CRC in orthotopic nude mice model. Mechanistically, the synergistic effects were at least partly mediated by inducing JNK mediated apoptosis and suppressing matrix metalloproteinases (MMPs) mediated invasion. Conclusions Hyperthermia in combination with TF‐targeted therapy could be a potential approach for CRC treatment. J. Surg. Oncol. 2012; 106:689–695. © 2012 Wiley Periodicals, Inc.