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山奈素通过抑制 PTEN/PI3K/AKT 信号通路发挥其在人胆囊癌细胞中的抗肿瘤作用。

Oroxylin A Exerts Its Antitumor Effects in Human Gallbladder Cancer via Inhibition of the PTEN/PI3K/AKT Signaling Pathway.

机构信息

Digestive Endoscopy Center, Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.

Department of Cholangio-pancreatic Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.

出版信息

Biol Pharm Bull. 2020;43(10):1511-1518. doi: 10.1248/bpb.b20-00262.

DOI:10.1248/bpb.b20-00262
PMID:32999161
Abstract

Gallbladder carcinoma (GBC) is one of the most common carcinomas of the biliary tract and is associated with aggressive malignancy and poor prognosis. Current therapeutic strategies, including surgery, radiotherapy, and chemotherapy, are not sufficient for the treatment of GBC, and new therapeutic strategies are urgently needed. The antitumor effects of oroxylin A (OrA), a natural flavonoid extracted from the dried roots of medicinal plants such as Scutellariae species (Radix Scutellariae), have been widely reported in various cancers. In this study, we first evaluated the antitumor activity and the underlying mechanism of action of OrA on GBC cells in vitro. Our results revealed that OrA significantly attenuated the proliferation, migration, and invasion of GBC cells, simultaneously promoting their apoptosis. Suppression of the phosphate on and tension homology deleted chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway was found to be the underlying mechanism involved in the antitumor activity of OrA. In addition, experiments using a tumor xenograft mouse model confirmed the antitumor effects of OrA in vivo. Taken together, our findings indicate that OrA could be a potential antitumor agent for the prospective treatment of GBC.

摘要

胆囊癌(GBC)是胆道系统最常见的癌之一,具有侵袭性恶性和预后不良的特点。目前的治疗策略,包括手术、放疗和化疗,不足以治疗 GBC,迫切需要新的治疗策略。氧杂蒽酮 A(OrA)是从黄芩等药用植物的干根中提取的一种天然黄酮类化合物,其在各种癌症中的抗肿瘤作用已被广泛报道。在这项研究中,我们首先评估了 OrA 在体外对 GBC 细胞的抗肿瘤活性及其作用机制。结果表明,OrA 可显著抑制 GBC 细胞的增殖、迁移和侵袭,同时促进其凋亡。抑制磷酸酶和张力蛋白同源缺失的染色体十号(PTEN)/磷酸肌醇-3 激酶(PI3K)/蛋白激酶 B(AKT)信号通路被发现是 OrA 抗肿瘤活性的作用机制。此外,使用肿瘤异种移植小鼠模型的实验证实了 OrA 在体内的抗肿瘤作用。综上所述,我们的研究结果表明,OrA 可能是一种有前途的治疗胆囊癌的潜在抗肿瘤药物。

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