International Journal of Oncology, 2015, 46(3):1131-40.

Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via PPARγ pathway

Mingzhi Song, Xiliang Tian, Ming Lu, et al

Department of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China

The peroxisome proliferator-activated receptor γ (PPARγ) is emerging as an important regulator in various metabolic processes of cancer. Genistein, as a major isoflavonoid isolated from dietary soybean, possesses a wide variety of biological activities, particularly, in cancer prevention. However, the mechanisms by which genistein elicits its growth inhibiting effects in osteosarcoma (OS) MG-63 cells have not been extensively elucidated. MG-63 cells were treated for 2 days with various concentrations of genistein and/or GW9662 (a selective antagonist of PPARγ). The effect of different drugs on cell viability was determined by Cell Counting Kit-8 (CCK-8). The assay of cell proliferation was performed using 5-ethynyl-2'-deoxyuridine (EdU). The changes of apoptosis and cell cycle progression were detected by flow cytometry experiments. The protein expression of PPARγ pathway (PPARγ, PTEN, BCL-2, Survivin, P21WAF1/CIP1 and Cyclin B1) was determined by western blot analysis. The expression of PPARγ and PTEN mRNA was detected by real-time quantitative RT-PCR analysis. We report that genistein caused OS cell growth inhibition. We found that the PPARγ expression in OS cells increased after genistein treatment. Further studies on the mechanisms of genistein revealed a series of cell growth changes related to the PPARγ pathway; while cell cycle changes can be reversed by GW9662. Genistein plays an important role in preventing OS cell growth, which can impede the OS cell cycle as a non-toxic activator of PPARγ, providing novel insights into the mechanisms of the therapeutic activities of genistein.

希腊《国际肿瘤学杂志》

金雀异黄素通过 PPARγ途径抑制人体骨肉瘤 MG-63 细胞的生长

大连医科大学第一附属医院骨科，辽宁大连116011;中国; 大连医科大学附属第一医院肝胆外科，辽宁大连116011，中国

过氧化物酶体增殖物激活受体γ（PPARγ）正在成为癌症各种代谢过程中的重要调节因子。染料木黄酮作为从膳食大豆分离的主要异黄酮，具有广泛的生物活性，特别是在癌症预防中。然而，染料木黄酮引起其在骨肉瘤（OS）MG-63细胞中的生长抑制作用的机制尚未得到广泛的阐明。用不同浓度的染料木素和/或GW9662（PPARγ的选择性拮抗剂）处理MG-63细胞2天。细胞计数Kit-8（CCK-8）测定不同药物对细胞活力的影响。使用5-乙炔基-2'-脱氧尿苷（EdU）进行细胞增殖的测定。通过流式细胞术实验检测凋亡和细胞周期进程的变化。通过蛋白质印迹分析确定PPARγ途径（PPARγ，PTEN，BCL-2，存活蛋白，P21WAF1 / CIP1和细胞周期蛋白B1）的蛋白表达。通过实时定量RT-PCR分析检测PPARγ和PTEN mRNA的表达。我们报道，染料木素引起OS细胞生长抑制。我们发现染料木素处理后，OS细胞中的PPARγ表达增加。关于染料木素的机理的进一步研究揭示了与PPARγ途径相关的一系列细胞生长变化;而细胞周期变化可以由GW9662逆转。染料木黄酮在预防OS细胞生长中起重要作用，可阻碍OS细胞周期作为PPARγ的无毒性激活因子，为染料木素的治疗活性机制提供新的见解。