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重楼皂苷E通过下调AKT/NF-κB信号通路抑制卵巢癌细胞的增殖、迁移和侵袭。

Polyphyllin E Inhibits Proliferation, Migration and Invasion of Ovarian Cancer Cells by Down-Regulating the AKT/NF-κB Pathway.

作者信息

Liu Yinglei, Cao Yang, Kai Haili, Han Yuwen, Huang Menghui, Gao Liusijie, Qiao Haifeng

机构信息

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nantong University.

出版信息

Biol Pharm Bull. 2022 May 1;45(5):561-568. doi: 10.1248/bpb.b21-00691. Epub 2022 Feb 19.

Abstract

Ovarian cancer has long been considered the second-highest cancer threat to women's reproductive system with high mortality. This is ascribed to the absence of highly efficient therapy and cancer metastasis. Accordingly, there is an urgent need for the development of new agents. Recently, Traditional Chinese medicine has gained extensive interest because of its safe use, validity, and distinct pharmacological effects. Polyphyllin E (PPE), as a major constituent in Rhizoma Paridis, is a promising cancer-fighting agent. However, the effect of PPE on ovarian cancers as well as associated latent mechanisms is still not completely understood. In this study, PPE was found to prohibit the proliferation of SK-OV-3 and OVCAR-3 ovarian cancer cells, causing marked cell death. Additionally, low-dose PPE could also inhibit motility and invasion of ovarian cancer cells. The mechanistic assessment revealed PPE-mediated matrix metalloproteinases, i.e., MMP2 and MMP9, inhibition via the AKT-nuclear factor kappa B (AKT/NF-κB) signaling pathway. Rescue experiments with transfection of AKT lentiviral particles remarkably reversed PPE inhibitory effects against ovarian cancer cells. In conclusion, PPE could inhibit proliferation of ovarian cancer cell migration and invasion by down-regulating the AKT/NF-κB pathway. Moreover, it has the potential to act as a novel agent for ovarian cancer treatment.

摘要

卵巢癌长期以来一直被认为是对女性生殖系统威胁第二大的癌症,死亡率很高。这归因于缺乏高效的治疗方法以及癌症转移。因此,迫切需要开发新的药物。最近,中药因其安全使用、有效性和独特的药理作用而受到广泛关注。重楼皂苷E(PPE)作为重楼的主要成分,是一种有前景的抗癌药物。然而,PPE对卵巢癌的作用及其相关潜在机制仍未完全了解。在本研究中,发现PPE可抑制SK-OV-3和OVCAR-3卵巢癌细胞的增殖,导致明显的细胞死亡。此外,低剂量PPE还可抑制卵巢癌细胞的运动性和侵袭性。机制评估显示,PPE通过AKT-核因子κB(AKT/NF-κB)信号通路介导基质金属蛋白酶(即MMP2和MMP9)的抑制。用AKT慢病毒颗粒转染进行的挽救实验显著逆转了PPE对卵巢癌细胞的抑制作用。总之,PPE可通过下调AKT/NF-κB通路抑制卵巢癌细胞的增殖、迁移和侵袭。此外,它有潜力作为一种新型的卵巢癌治疗药物。

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