Background

Recently, accumulating evidence has proved that apoptosis and oxidative stress exert essential roles in the development of polycystic ovarian syndrome (PCOS). Besides, multiple natural products have been identified to be related to the PCOS process.

Objective

This investigation aimed to elucidate the effects and mechanisms of lycopene on granulosa-like tumor cell line (KGN) in the presence of dihydrotestosterone (DHT). KGN cells were treated using DHT or lycopene and cell survival rate was tested by cell counting kit 8 (CCK-8) assay. Also, flow cytometry, western blot as well as enzyme-linked immunosorbent assay (ELISA) were utilized to detect cell apoptosis, protein level and the marker of oxidative stress. ROS accumulation was observed with DCFH-DA dye. The nuclear factor-erythroid 2-related factor (Nrf2) expression in KGN cells was reduced via small interfering RNA (siRNA). The nuclear translocation of Nrf2 was determined through immunofluorescence (IF) analysis.

Results

Lycopene effectively reversed DHT-induced apoptosis in addition to oxidative stress in KGN cells. Besides, lycopene treatment obviously activated Nrf2 signaling and accelerated nuclear translocation of Nrf2 in KGN cells. Nrf2 depletion partially counteracted the role of lycopene in DHT-mediated apoptosis as well as oxidative stress in KGN cells.

Conclusion

In summary, this work revealed that lycopene alleviates oxidative stress and apoptosis in KGN cells in the presence of DHT, which at least partly by depending on the activation of Nrf2 cascade signal at the molecular level.

中文翻译：

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番茄红素通过调节 Nrf2 通路减轻 DHT 诱导的人颗粒细胞系 KGN 细胞凋亡和氧化应激

背景

近年来，越来越多的证据证明细胞凋亡和氧化应激在多囊卵巢综合征（PCOS）的发生发展中发挥重要作用。此外，多种天然产物已被确定与多囊卵巢综合症过程有关。

客观的

本研究旨在阐明番茄红素在二氢睾酮 (DHT) 存在下对颗粒样肿瘤细胞系 (KGN) 的影响和机制。使用 DHT 或番茄红素处理 KGN 细胞，并通过细胞计数试剂盒 8 (CCK-8) 测定法测试细胞存活率。此外，还利用流式细胞术、蛋白质印迹以及酶联免疫吸附测定（ELISA）来检测细胞凋亡、蛋白水平和氧化应激标志物。用 DCFH-DA 染料观察到 ROS 积累。通过小干扰 RNA (siRNA) 减少 KGN 细胞中核因子 - 红细胞 2 相关因子 (Nrf2) 的表达。通过免疫荧光 (IF) 分析确定 Nrf2 的核转位。

结果

除了 KGN 细胞的氧化应激外，番茄红素还能有效逆转 DHT 诱导的细胞凋亡。此外，番茄红素处理明显激活了Nrf2信号并加速了KGN细胞中Nrf2的核转位。 Nrf2 缺失部分抵消了番茄红素在 DHT 介导的细胞凋亡以及 KGN 细胞氧化应激中的作用。

结论

总之，这项工作表明，在 DHT 存在的情况下，番茄红素可以减轻 KGN 细胞的氧化应激和细胞凋亡，这至少部分依赖于分子水平上 Nrf2 级联信号的激活。