期刊
CANCER LETTERS
卷 418, 期 -, 页码 196-203出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.01.009
关键词
Chemokine receptor 4 (CXCR4); AMD3100; Triple-negative breast cancer; Radiatiosensiticity; Apoptosis
类别
资金
- National Natural Science Foundation of China [81671750]
- National Natural Science Foundation of Guangdong province [2016A030312008]
- Projects of International Cooperation and Exchanges NSFC [81320108015]
- Shantou University Medical College Clinical Research Enhancement Initiative of China [201422]
- Guangdong Provincial Key Laboratory on Breast Cancer Diagnosis and Treatment Research
Radiation therapy (RT) is one of the primary modalities for triple-negative breast cancer (TNBC) treatment. However, due to the pro-metastatic potential of radiation and the intrinsic radiation resistance of some tumors, many patients experience RT failure, which leads to cancer relapse and distant metastasis. This preclinical study evaluated the efficacy of the antagonist of the SDF-1 receptor CXCR4, AMD3100, as a radiosensitizer in TNBC models. The combined effect of ionizing radiation and AMD3100 was determined in vitro by surviving fraction, cell cycle distribution, Bax and Bcl-2 expression, and apoptosis assays in a TNBC cell line (MDA-MB-231). For in vivo studies, human xenograft athymic nude mice were used. Treatment of TNBC cells with AMD3100 significantly augmented cellular radiosensitivity. Radio sensitivity was enhanced specifically through increased Bax expression, reduced Bcl-2 expression, prolonged G2-M arrest, and increased apoptosis. Combined treatment with AMD3100 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.5 to 1.8. These findings support the evaluation of antagonists of the SDF-1 receptor CXCR4, such as AMD3100, as potent radio sensitizers in TNBC. (C) 2018 Elsevier B.V. All rights reserved.
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