Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.
Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.
复制标题
双氢青蒿素抑制胆囊癌TCTP依赖性转移
DOI：
10.1186/s13046-017-0531-3
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发表时间：
2017-05-15
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Zhang F;Ma Q;Xu Z;Liang H;Li H;Ye Y;Xiang S;Zhang Y;Jiang L;Hu Y;Wang Z;Wang X;Zhang Y;Gong W;Liu Y
背景转移性或复发性胆囊癌患者通常预后较差。因此，靶向转移是治疗胆囊癌的治疗策略之一。方法采用免疫组织化学染色法检测胆囊癌样本中翻译控制肿瘤蛋白(TCTP)的水平。伤口愈合、迁移和侵袭测定用于研究细胞的运动性。 Western blot 检测用于研究 TCTP 和其他蛋白质的水平。建立肝转移模型和肺转移模型，探讨双氢青蒿素对胆囊癌转移的抑制作用。结果TCTP在胆囊癌患者中异常表达，与转移和不良预后相关。消耗 TCTP 显着抑制胆囊癌细胞迁移和侵袭。我们发现双氢青蒿素作为 TCTP 的有效抑制剂，通过减少细胞分裂控制蛋白 42 同源物 (Cdc42) 的激活来抑制 TCTP 依赖性细胞迁移和侵袭。此外，在患有异种移植肿瘤的小鼠中，双氢青蒿素治疗减少了胆囊癌细胞转移并提高了生存率。结论这些发现为双氢青蒿素治疗胆囊癌转移的治疗活性提供了新的见解。
BackgroundPatients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.MethodsLevels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.ResultsTCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.ConclusionsThese findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.