Nadal-Serrano Mercedes, Sastre-Serra Jorge, Valle Adamo, Roca Pilar, Oliver Jordi
Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les IllesBalears, E07122 Palma de Mallorca, Illes Balears, Spain.
Cell Physiol Biochem. 2015;36(1):221-32. doi: 10.1159/000374066. Epub 2015 Apr 30.
BACKGROUND/AIMS: Large-scale epidemiological studies support a correlation between obesity and breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play a significant role in mammary tumor formation and progression. Moreover, regulation of oxidative stress is another important factor in both tumor development and responses to anticancer therapies. The aim of this study was to examine the relationship between oxidative stress and chronic leptin exposure.
We treated MCF-7 breast cancer cells with 100 ng/mL leptin for 10 days and analyzed cell growth, ROS production and oxidative damage, as well as, some of the main antioxidant systems. Furthermore, since the hyperleptinemia has been associated with a worse pathology prognosis, we decided to test the influence of leptin in response to cisplatin anticancer treatment.
Leptin signalling increased cell proliferation but reduced ROS production, as well as, oxidative damage. We observed an upregulation of SIRT1 after leptin exposure, a key regulator of stress response and metabolism. Additionally, leptin counteracted cisplatin-induced cytotoxicity in tumor cells, showing a decrease in cell death.
Chronic leptin could contribute to the effective regulation of endogenous and treatment-induced oxidative stress, and it contributes to explain in part its proliferative effects.
背景/目的：大规模流行病学研究支持绝经后女性肥胖与乳腺癌之间存在关联。肥胖者循环瘦素水平升高，且有人认为其在乳腺肿瘤形成和进展中起重要作用。此外，氧化应激调节是肿瘤发生发展及抗癌治疗反应的另一个重要因素。本研究旨在探讨氧化应激与长期瘦素暴露之间的关系。
我们用100 ng/mL瘦素处理MCF-7乳腺癌细胞10天，分析细胞生长、活性氧（ROS）产生和氧化损伤，以及一些主要的抗氧化系统。此外，由于高瘦素血症与较差的病理预后相关，我们决定测试瘦素对顺铂抗癌治疗反应的影响。
瘦素信号增强细胞增殖，但减少ROS产生及氧化损伤。瘦素暴露后我们观察到SIRT1上调，SIRT1是应激反应和代谢的关键调节因子。此外，瘦素抵消了顺铂诱导的肿瘤细胞毒性，细胞死亡减少。
长期瘦素可能有助于对内源性和治疗诱导的氧化应激进行有效调节，这在一定程度上解释了其增殖作用。
