“Iron-saturated-bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice

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• 作者：Xueying Sun (1) (3)
  Ruohan Jiang (1)
  Aneta Przepiorski (1)
  Shiva Reddy (1)
  Kate P Palmano (2)
  Geoffrey W Krissansen (1)
  
• 关键词：Breast cancer ; Iron ; saturated lactoferrin ; Tamoxifen ; Immune enhancement ; Mice
• 刊名：BMC Cancer
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：12
• 期：1
• 全文大小：459KB
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  60. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/591/prepub
  
• 作者单位：Xueying Sun (1) (3)
  Ruohan Jiang (1)
  Aneta Przepiorski (1)
  Shiva Reddy (1)
  Kate P Palmano (2)
  Geoffrey W Krissansen (1)
  
  1. Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1005, New Zealand
  3. Department of General Surgery, The Hepatosplenic Surgery Center, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
  2. Fonterra Research Centre, Palmerston North, 4442, New Zealand
  
• ISSN：1471-2407

文摘

Background Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers. Methods In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5?mg/Kg) were fed an Fe-Lf supplemented diet (5?g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed. Results Tamoxifen weakly (IC50?~-?μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations in vitro. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4?day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P-lt;-.001), respectively, compared to untreated controls. The combination therapy was significantly (all P-lt;-.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors. Conclusions The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.