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Correction published on 8 March 2019, see Cancers 2019, 11(3), 335.

Open AccessArticle
Cancers 2018, 10(10), 386; https://doi.org/10.3390/cancers10100386

Nafamostat Mesilate Enhances the Radiosensitivity and Reduces the Radiation-Induced Invasive Ability of Colorectal Cancer Cells

1
Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan
2
Division of Gene Therapy, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan
3
Division of Medical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan
*
Author to whom correspondence should be addressed.
Received: 19 September 2018 / Revised: 12 October 2018 / Accepted: 15 October 2018 / Published: 17 October 2018
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
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Abstract

Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for patients with locally advanced low rectal cancer. However, several studies have reported that ionizing radiation (IR) activates nuclear factor kappa B (NF-κB) that causes radioresistance and induces matrix metalloproteinase (MMP)-2/-9, which promote tumor migration and invasion. Nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, enhances the chemosensitivity to cytotoxic agents in digestive system cancer cells by inhibiting NF-κB activation. Therefore, we evaluated the combined effect of IR and FUT175 on cell proliferation, migration and invasion of colorectal cancer (CRC) cells. IR-induced upregulation of intranuclear NF-κB, FUT175 counteracted this effect. Moreover, the combination treatment suppressed cell viability and induced apoptosis. Similar effects were also observed in xenograft tumors. In addition, FUT175 prevented the migration and invasion of cancer cells caused by IR by downregulating the enzymatic activity of MMP-2/-9. In conclusion, FUT175 enhances the anti-tumor effect of radiotherapy through downregulation of NF-κB and reduces IR-induced tumor invasiveness by directly inhibiting MMP-2/-9 in CRC cells. Therefore, the use of FUT175 during radiotherapy might improve the efficacy of radiotherapy in patients with CRC. View Full-Text
Keywords: nafamostat mesilate; colorectal cancer; ionizing radiation; NF-κB; matrix metalloproteinases nafamostat mesilate; colorectal cancer; ionizing radiation; NF-κB; matrix metalloproteinases
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Sugano, H.; Shirai, Y.; Horiuchi, T.; Saito, N.; Shimada, Y.; Eto, K.; Uwagawa, T.; Ohashi, T.; Yanaga, K. Nafamostat Mesilate Enhances the Radiosensitivity and Reduces the Radiation-Induced Invasive Ability of Colorectal Cancer Cells. Cancers 2018, 10, 386.

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