Maleki Jafar, Nourbakhsh Mitra, Shabani Mohammad, Korani Mohsen, Nourazarian Seyed Manuchehr, Ostadali Dahaghi Mohammad Reza, Moghadasi Mohamad Hossein
Department of Biochemistry, Iran University of Medical Sciences, Tehran, IR Iran.
Department of Biochemistry, Iran University of Medical Sciences, Tehran, IR Iran ; Metabolic Disorders Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran.
Iran J Cancer Prev. 2015 May;8(3):e2332. doi: 10.17795/ijcp2332. Epub 2015 May 22.
Experimental and epidemiological evidence supports a role for steroid hormones in the pathogenesis of ovarian cancer. Among steroid hormones, 17β-estradiol (E2) has the most potent effect on proliferation, apoptosis and metastasis.
In the present study, we investigated the effect of E2 on production of ROS and NO in ovarian cancer cells.
Ovarian adenocarcinoma cell line (OVCAR-3) was cultured and treated with various concentrations of E2, antioxidants (N-acetyle cysteine and Ebselen) and ICI182780 as an estrogen receptor antagonist. MTT test was performed to evaluate cell viability. NO and ROS levels were measured by Griess and DCFH-DA methods, respectively.
ROS levels as well as NO levels were increased in OVCAR-3 cells treated with E2. The increase in ROS production was in parallel with increased cell viability which indicates that estrogen-induced ROS can participate in cancer progression. ICI182780 abolished E2-induced ROS production. Progesterone was also effective in reducing ROS and NO generation.
NO and ROS are important molecules in signaling networks in cell. These molecules can be used as therapeutic targets for prevention and treatment of ovary cancer and other estrogen-induced malignancies.
实验和流行病学证据支持类固醇激素在卵巢癌发病机制中的作用。在类固醇激素中，17β-雌二醇（E2）对增殖、凋亡和转移具有最显著的影响。
在本研究中，我们调查了E2对卵巢癌细胞中活性氧（ROS）和一氧化氮（NO）产生的影响。
培养卵巢腺癌细胞系（OVCAR-3），并用不同浓度的E2、抗氧化剂（N-乙酰半胱氨酸和依布硒仑）以及雌激素受体拮抗剂ICI182780进行处理。进行MTT试验以评估细胞活力。分别采用Griess法和DCFH-DA法测量NO和ROS水平。
用E2处理的OVCAR-3细胞中ROS水平和NO水平均升高。ROS产生的增加与细胞活力的增加平行，这表明雌激素诱导的ROS可参与癌症进展。ICI182780消除了E2诱导的ROS产生。孕酮在降低ROS和NO生成方面也有效。
NO和ROS是细胞信号网络中的重要分子。这些分子可作为预防和治疗卵巢癌及其他雌激素诱导的恶性肿瘤的治疗靶点。
