Department of Obstetrics and Gynecology, Dong-A University, College of Medicine, Busan 602-715, Republic of Korea.
Int J Mol Med. 2012 Nov;30(5):1211-8. doi: 10.3892/ijmm.2012.1104. Epub 2012 Aug 20.
Endometrial cancer is a significant malignancy in developed countries. Unopposed estrogen stimulation is considered as an important risk factor for endometrial cancer. Epigallocathechin-3-gallate (EGCG), biological active component of green tea, inhibits cancer cell proliferation. However, it is unknown whether EGCG has anticancer effects on endometrial cancer and what the molecular mechanism(s) are. We investigated the anticancer effects of EGCG on a human endometrial adenocarcinoma cell line (Ishikawa cells) with or without 17β-estradiol (E2) treatment. Cell proliferation assay was performed using 3-(4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide (MTT). The cell cycle was determined by flow cytometry and real-time analysis of cyclin and cdk genes. The apoptosis was measured by Annexin V-PI staining and real-time analysis of bcl-2, Bax and caspase genes. The MAPK signal, Akt and caspase-3 were determined by immunoblotting. Decreased estrogen and progesterone receptor expression was observed in EGCG-treated Ishikawa cells, and decreased MAPK signals and phospho-Akt were observed as well. EGCG caused the arrest of cells in the G0/G1 phase of the cell cycle. This compound interfered with Akt activation and MAPK signals, and increased apoptosis signals leading to a controlled caspases, Bcl-2, Bax genes and protein expression. Taken together, EGCG inhibits cell proliferation and induces apoptosis through Akt and MAPK signals. These findings suggest that EGCG may exert growth-inhibitory and apoptosis-inducing effects on endometrial cancer cells, accompanied by decreased estrogen and progesterone receptor. EGCG may have future clinical implications with respect to the development of novel approaches as an adjuvant therapy in endometrial cancer.
子宫内膜癌是发达国家的一种重要恶性肿瘤。雌激素的拮抗刺激被认为是子宫内膜癌的一个重要危险因素。表没食子儿茶素没食子酸酯（EGCG）是绿茶中的一种生物活性成分，可抑制癌细胞增殖。然而，目前尚不清楚 EGCG 是否对子宫内膜癌具有抗癌作用，以及其分子机制是什么。我们研究了 EGCG 对人子宫内膜腺癌细胞系（Ishikawa 细胞）的抗癌作用，该细胞系在有无 17β-雌二醇（E2）处理的情况下进行研究。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（MTT）进行细胞增殖试验。通过流式细胞术和细胞周期蛋白和细胞周期蛋白依赖性激酶基因的实时分析来确定细胞周期。通过 Annexin V-PI 染色和实时分析 bcl-2、Bax 和 caspase 基因来测量细胞凋亡。通过免疫印迹测定 MAPK 信号、Akt 和 caspase-3。在 EGCG 处理的 Ishikawa 细胞中观察到雌激素和孕激素受体表达降低，并且观察到 MAPK 信号和磷酸化 Akt 降低。EGCG 导致细胞在细胞周期的 G0/G1 期停滞。该化合物干扰 Akt 激活和 MAPK 信号，并增加凋亡信号，导致 caspase 、Bcl-2、Bax 基因和蛋白表达受到控制。总之，EGCG 通过 Akt 和 MAPK 信号抑制细胞增殖并诱导细胞凋亡。这些发现表明，EGCG 可能对子宫内膜癌细胞发挥生长抑制和诱导凋亡作用，同时降低雌激素和孕激素受体。EGCG 可能对子宫内膜癌的治疗具有未来的临床意义，可作为辅助治疗的新方法。
