Peroxisome Proliferator- Activated Receptor-gamma and Nuclear Factor-kappa B in Obese Breast Cancer Patients: Correlation with Omega-3 polyunsaturated Fatty Acids with Adjuvant Chemotherapy

I. Sharaf, M. Kamel, R. El-Tahan, H. Kohail, M. E. Naggar
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Abstract

Background: PPAR-γ has been reported to affect cell proliferation/differentiation pathways in various malignancies. PPAR-γ negatively regulates NFκB gene which is important in breast cancer progression. Objective: The present study was designed to evaluate the relationship between PPAR-γ and NF-κB and the clinicopathological parameters of breast cancer women. The possible effects of adjuvant omega-3 fatty acid treatment with chemotherapy was also studied. Methods: 40 obese breast cancer patients was subdivided into two groups(20 each),chemo group received chemotherapy alone and omega group received 2 gm n-3 daily wih chemotherapy and control group included 20 obese women. Serum PPAR-γ and NF-κB levels were conducted for all the studied groups. Results: PPAR-γ was significantly lower than control .The level was decreased with increased positivity of ER, PR and increased with Her-2/neu in preand postmenopausal breast cancer patients. NF-κB significantly higher than controls and decreased with the increased positivity of ER, PR and Her-2/neu in preand postmenopausal breast cancer patients. Omega-3 FAs treatment with chemotherapy significantly enhances the level of PPAR-γ and decreases NF-κB level. Conclusion: The using of omega-3 PUFA as adjuvant treatment may increase sensitivity of cancer cells for chemotherapy by targeting PPAR-γ /NF-κB signaling pathway through correction of their derangements.
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肥胖乳腺癌患者的过氧化物酶体增殖物活化受体γ和核因子κ B:与Omega-3多不饱和脂肪酸与辅助化疗的相关性
背景:PPAR-γ已被报道影响多种恶性肿瘤的细胞增殖/分化途径。PPAR-γ负调控NFκB基因在乳腺癌进展中起重要作用。目的:探讨PPAR-γ和NF-κB与乳腺癌患者临床病理参数的关系。同时还研究了辅助omega-3脂肪酸治疗化疗的可能效果。方法:将40例肥胖乳腺癌患者再分为两组,每组20例,化疗组单独化疗,omega组每日给予2 gm n-3并化疗,对照组20例肥胖女性。测定各组大鼠血清PPAR-γ和NF-κB水平。结果:绝经前和绝经后乳腺癌患者PPAR-γ水平显著低于对照组,随ER、PR阳性升高而降低,随Her-2/neu阳性升高而升高。绝经前和绝经后乳腺癌患者NF-κB水平显著高于对照组,并随着ER、PR和Her-2/neu阳性水平的升高而降低。Omega-3 FAs联合化疗可显著提高PPAR-γ水平,降低NF-κB水平。结论:使用omega-3 PUFA作为辅助治疗可能通过靶向PPAR-γ /NF-κB信号通路,纠正其紊乱,提高癌细胞对化疗的敏感性。
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