کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8447442 | 1547188 | 2011 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Triple-negative breast cancers, which represent 10-20% of all mammary tumours, are characterised by the aggressive phenotype, are often found in younger women and have been associated with poor prognosis. Obesity increases the risk for triple-negative breast cancer development. Because triple-negative breast cancer patients are unresponsive to current targeted therapies and other treatment options are only partially effective, new pharmacological modalities are urgently needed. Here we examined if the leptin (obesity hormone) receptor is a viable target for the treatment of this cancer subtype. In human triple-negative breast cancer tissues, the leptin receptor was expressed in 92% (64/69) and leptin in 86% (59/69) of cases. In a model triple-negative breast cancer cell line MDA-MB-231, the leptin receptor antagonist peptide Allo-aca inhibited leptin-induced proliferation at 50Â pM concentration. In an MDA-MB-231 orthotopic mouse xenograft model, Allo-aca administered subcutaneously significantly extended the average survival time from 15.4Â days (untreated controls) to 24 and 28.1Â days at 0.1 and 1Â mg/kg/day doses, respectively. In parallel, conventional treatment with 1Â mg/kg/day intraperitoneal cisplatin prolonged the average survival time to 18.6Â days, while administration of 20Â mg/kg/day oral Tamoxifen (negative control) had no significant survival effects relative to controls. In normal CD-1 mice, Allo-aca produced no systemic toxicity up to the highest studied subcutaneous bolus dose of 50Â mg/kg, while, as expected, it induced a modest 6-10% body weight increase. Our results indicate that leptin receptor antagonists could become attractive options for triple-negative breast cancer treatment, especially in the obese patient population.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 47, Issue 10, July 2011, Pages 1578-1584
Journal: European Journal of Cancer - Volume 47, Issue 10, July 2011, Pages 1578-1584
نویسندگان
Laszlo Jr., Ilona Kovalszky, Mirko Riolfi, Rita Ferla, Julia Olah, Andras Sztodola, Kaushik Nama, Annamaria Molino, Quirino Piubello, John D. Wade, Eva Surmacz,