Glycyrrhetinic acid (GA) is a major bioactive compound of licorice. The objective of this study was to investigate the effects of GA on ovarian cancer, particularly those related to angiogenesis and apoptosis, and to elucidate the underlying mechanisms of action. In vitro studies showed that GA significantly inhibited proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. GA inhibited the phosphorylation of major receptors and enzymes involved in angiogenesis, such as VEGFR2, mTOR, Akt, ERK1/2, MEK1/2, p38 and JNK1/2 in HUVECs. In addition, GA induced apoptosis, loss of mitochondrial membrane potential and cell cycle arrest in G1 phase in A2780 ovarian cancer cells. The proapoptotic effect of GA involved the increased phosphorylation of p38 and JNK1/2; increased cleavage of caspase 3, caspase 9 and PARP; reduced phosphorylation of mTOR, Akt and ERK1/2; and reduced expressions of survivin and cyclin D1. Ex vivo studies showed that GA significantly inhibited microvessel sprouting in rat aortic ring model. In vivo studies showed that GA inhibited the formation of new blood vessels in zebrafish and mouse Matrigel plug. GA also significantly reduced the size of ovarian cancer xenograft tumors in nude mice. Taken together, GA possesses potential antitumor effects, and the underlying mechanisms may involve the inhibition of signaling pathways related to angiogenesis and the activation of apoptotic pathways in cancer cells. Our findings suggest that GA could serve as an effective regimen in the prevention or treatment of cancer.

甘草次酸（GA）是甘草的主要生物活性化合物。这项研究的目的是研究GA对卵巢癌的影响，尤其是与血管生成和细胞凋亡有关的卵巢癌的影响，并阐明其潜在的作用机制。体外研究表明，GA以浓度依赖的方式显着抑制人脐静脉内皮细胞（HUVEC）的增殖，迁移，侵袭和管形成。GA抑制HUVEC中与血管生成有关的主要受体和酶（如VEGFR2，mTOR，Akt，ERK1 / 2，MEK1 / 2，p38和JNK1 / 2）的磷酸化。此外，GA诱导了A2780卵巢癌细胞的凋亡，线粒体膜电位的丧失以及G1期的细胞周期停滞。GA的促凋亡作用涉及p38和JNK1 / 2磷酸化的增加。半胱天冬酶3，半胱天冬酶9和PARP的切割增加；降低了mTOR，Akt和ERK1 / 2的磷酸化；降低survivin和cyclin D1的表达。离体研究表明，GA显着抑制了大鼠主动脉环模型中的微血管发芽。体内研究表明，GA抑制了斑马鱼和小鼠基质胶塞中新血管的形成。GA还显着减少了裸鼠卵巢癌异种移植肿瘤的大小。综上，GA具有潜在的抗肿瘤作用，其潜在机制可能涉及抑制与血管生成有关的信号传导途径和激活癌细胞中的凋亡途径。我们的发现表明，GA可以作为预防或治疗癌症的有效方案。