Xuzhou City Hospital of Chinese Medicine, Xuzhou, Jiangsu, 221009, China.
Department of Obstetrics and Gynecology, Lishui Hospital of Chinese Medicine, Lishui, Zhejiang, 323000, China.
Biochem Biophys Res Commun. 2021 Mar 19;545:81-88. doi: 10.1016/j.bbrc.2021.01.028. Epub 2021 Feb 3.
Cervical cancer remains the leading cause of cancerous death among women worldwide. Oleanolic acid (OA) is a substance that occurs naturally in the leaves, fruits, and rhizomes of plants and has anti-cancer activity. In this study, tumor-bearing mice were used as the animal model and Hela cells were used as cellular model. In vivo experiments have showed that OA significantly reduced the size and mass of cervical cancer tumors in mice. In vitro experiments have showed that OA significantly reduced the viability and proliferative capacity of Hela cells. In both in vivo and in vitro assays, OA increased the oxidative stress levels and Fe content, and increased the expression of ferroptosis-related proteins. We found that ACSL4 was highly expressed in both xenograft models and cervical carcinoma cells with OA treatment. Further use of siRNA to interfere with ACSL4 expression in cervical cancer cells revealed that the inhibitory effect of OA on cell viability and proliferative capacity was counteracted, while a decrease in ROS levels and GPX4 was detected, suggesting that OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer.
宫颈癌仍然是全球女性癌症死亡的主要原因。齐墩果酸（OA）是一种天然存在于植物的叶、果实和根茎中的物质，具有抗癌活性。在这项研究中，使用荷瘤小鼠作为动物模型，使用 Hela 细胞作为细胞模型。体内实验表明，OA 显著降低了荷瘤小鼠宫颈癌肿瘤的大小和质量。体外实验表明，OA 显著降低了 Hela 细胞的活力和增殖能力。在体内和体外实验中，OA 均增加了氧化应激水平和铁含量，并增加了铁死亡相关蛋白的表达。我们发现 ACSL4 在异种移植模型和经 OA 处理的宫颈癌细胞中均高表达。进一步使用 siRNA 干扰宫颈癌细胞中 ACSL4 的表达，发现 OA 对细胞活力和增殖能力的抑制作用被抵消，同时检测到 ROS 水平和 GPX4 降低，表明 OA 通过促进 ACSL4 表达激活了 Hela 细胞中的铁死亡，从而降低了 Hela 细胞的存活率。因此，OA 通过促进 ACSL4 依赖性铁死亡可能是治疗宫颈癌的一种潜在方法。
