双氢青蒿素抑制胆囊癌中TCTP依赖的转移。

Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer.

作者信息

Zhang Fei, Ma Qiang, Xu Zihang, Liang Haibin, Li Huaifeng, Ye Yuanyuan, Xiang Shanshan, Zhang Yijian, Jiang Lin, Hu Yunping, Wang Zheng, Wang Xuefeng, Zhang Yong, Gong Wei, Liu Yingbin

机构信息

Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Room 517, Building 22, Xinhua Hospital, 1665 Kongjiang Rd., Shanghai, 200092, China.

Shanghai Research Center of Biliary Tract Disease, 1665 Kongjiang Road, Shanghai, 200092, China.

出版信息

J Exp Clin Cancer Res. 2017 May 15;36(1):68. doi: 10.1186/s13046-017-0531-3.

BACKGROUND

Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.

METHODS

Levels 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.

RESULTS

TCTP 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.

CONCLUSIONS

These findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.

背景

转移性或复发性胆囊癌患者的预后通常较差。因此，靶向转移是治疗胆囊癌的治疗策略之一。

方法

通过免疫组织化学染色测量胆囊癌样本中翻译控制肿瘤蛋白（TCTP）的水平。采用伤口愈合、迁移和侵袭实验来研究细胞的运动能力。蛋白质印迹法用于检测TCTP和其他蛋白质的水平。建立肝转移模型和肺转移模型来研究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，与转移及不良预后相关。敲低TCTP可显著抑制胆囊癌细胞的迁移和侵袭。我们发现，双氢青蒿素作为TCTP的有效抑制剂，通过降低细胞分裂控制蛋白42同源物（Cdc42）的活性来抑制TCTP依赖的细胞迁移和侵袭。此外，在异种移植瘤小鼠中，双氢青蒿素治疗可减少胆囊癌细胞转移并提高生存率。