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紫草素通过 JNK 信号通路诱导胆囊癌细胞凋亡和 G0/G1 期阻滞。

Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via the JNK signaling pathway.

机构信息

Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.

出版信息

Oncol Rep. 2017 Dec;38(6):3473-3480. doi: 10.3892/or.2017.6038. Epub 2017 Oct 17.

DOI:10.3892/or.2017.6038
PMID:29039581
Abstract

Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with few curative therapeutic stragegies and poor prognosis. In the present study, we detected the effects of shikonin on GBC cells as well as the underlying molecular mechanisms. The results demonstrated that GBC cell proliferation was inhibited by shikonin as determined by MTT and colony formation assays. Flow cytometry results demonstrated that shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC cells. Western blot assay showed that shikonin induced mitochondrial-dependent apoptosis via the JNK signaling pathway. Moreover, shikonin suppressed tumor growth in mice bearing GBC-derived xenografts in a dose‑dependent manner without side-effects. These results revealed that shikonin exhibits anticancer effects on GBC cells by inducing apoptosis and regulating the cell cycle. Taken together, shikonin may be a novel and safe chemotherapeutic agent for the treatment of GBC.

摘要

紫草素是从紫草的根部提取的一种天然产物,被认为具有抗肿瘤作用。胆囊癌(GBC)是一种常见的胆道恶性肿瘤,治疗策略有限,预后较差。在本研究中,我们检测了紫草素对 GBC 细胞的作用及其潜在的分子机制。结果表明,MTT 和集落形成实验表明,紫草素抑制 GBC 细胞增殖。流式细胞术结果表明,紫草素通过 JNK 信号通路诱导细胞凋亡并促进 G0/G1 期阻滞。Western blot 实验表明,紫草素通过线粒体依赖性凋亡途径诱导细胞凋亡。此外,紫草素以剂量依赖的方式抑制携带 GBC 衍生异种移植物的小鼠的肿瘤生长,无副作用。这些结果表明,紫草素通过诱导细胞凋亡和调节细胞周期对 GBC 细胞发挥抗癌作用。综上所述,紫草素可能是治疗 GBC 的一种新型、安全的化疗药物。

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