Tian Shuang, Ren Lili, Liu Chao, Wang Zhe
Department of Pathology, College of Integrated Chinese and Western Medical, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Department of Cell Biology and Genetics, Basic Medical College, Jinzhou Medical University, Jinzhou 121001, China.
Molecules. 2024 Feb 21;29(5):939. doi: 10.3390/molecules29050939.
Atractylenolide II (AT-II), the major bioactive compound of , exhibits anti-cancer activity against many types of tumors, but the roles and the potential mechanisms in endometrial cancer remain unclear. In the present study, AT-II treatment was found to significantly suppress RL95-2 and AN3CA cell proliferation and glycolysis, and induced their apoptosis by inactivating the ERK signaling pathway, accompanied by the changing expression of the glycolytic key enzymes and apoptotic-related proteins. Peptidyl arginine deiminase 3 (PADI3), as the candidate target gene of AT-II, was highly expressed in the endometrial cancer tissues and associated with a poor prognosis according to bioinformatics analysis. PADI3 knockdown inhibited proliferation and glycolysis in endometrial cancer cells and induced cell apoptosis. Furthermore, AT-II negatively regulated the expression of PADI3, and PADI3 overexpression reversed the effects of AT-II on endometrial cancer cells. Our findings suggested that the anti-cancer function of AT-II is associated with the suppression of glycolysis and induction of apoptosis by blocking the PADI3-ERK signaling pathway. Thus, AT-II represents a novel therapeutic target for endometrial cancer and targeting AT-II may serve as a potential strategy for the clinical therapy of endometrial cancer.
白术内酯II（AT-II）是[植物名称未给出]的主要生物活性化合物，对多种类型的肿瘤具有抗癌活性，但在子宫内膜癌中的作用及潜在机制仍不清楚。在本研究中，发现AT-II处理可显著抑制RL95-2和AN3CA细胞增殖及糖酵解，并通过使ERK信号通路失活诱导其凋亡，同时伴随着糖酵解关键酶和凋亡相关蛋白表达的变化。肽基精氨酸脱亚氨酶3（PADI3）作为AT-II的候选靶基因，在子宫内膜癌组织中高表达，且根据生物信息学分析与预后不良相关。敲低PADI3可抑制子宫内膜癌细胞的增殖和糖酵解并诱导细胞凋亡。此外，AT-II负向调节PADI3的表达，而PADI3过表达可逆转AT-II对子宫内膜癌细胞的作用。我们的研究结果表明，AT-II的抗癌功能与通过阻断PADI3-ERK信号通路抑制糖酵解和诱导凋亡有关。因此，AT-II代表了子宫内膜癌的一个新的治疗靶点，靶向AT-II可能作为子宫内膜癌临床治疗的一种潜在策略。
