Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models

Leu,Jyh‑Der; Wang,Bo‑Shen; Chiu,Shu‑Jun; Chan,Chun‑Yuan; Chen,Chien‑Chih; Chen,Fu‑Du; Avirmed,Shiirevnyamba; Lee,Yi‑Jang

doi:10.3892/ol.2016.5345

Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models

Authors:
- Jyh‑Der Leu
- Bo‑Shen Wang
- Shu‑Jun Chiu
- Chun‑Yuan Chan
- Chien‑Chih Chen
- Fu‑Du Chen
- Shiirevnyamba Avirmed
- Yi‑Jang Lee
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Affiliations: Department of Radiation Oncology, Taipei City Hospital, Renai Branch, Da'an, Taipei 106, Taiwan, R.O.C., Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Engineering, National Yang‑Ming University, Beitou, Taipei 112, R.O.C., Department of Life Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C., Department of Family Medicine, Taipei City Hospital, Renai Branch, Da'an, Taipei 112, Taiwan, R.O.C., Department of Electronic Engineering, Hwa‑Hsia University of Technology, Zhonghe, Taipei 235, Taiwan, R.O.C., Department of Surgery, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
Published online on: November 2, 2016 https://doi.org/10.3892/ol.2016.5345
Pages: 4975-4982
Copyright: © Leu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti‑inflammatory, antiangiogenic, anti‑invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT‑26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT‑26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2‑Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2‑Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin‑null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin‑null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

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