Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer

Abstract 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...

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Main Authors: Fei Zhang, Qiang Ma, Zihang Xu, Haibin Liang, Huaifeng Li, Yuanyuan Ye, Shanshan Xiang, Yijian Zhang, Lin Jiang, Yunping Hu, Zheng Wang, Xuefeng Wang, Yong Zhang, Wei Gong, Yingbin Liu
Format: Article
Language:English
Published: BMC 2017-05-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13046-017-0531-3
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author Fei Zhang
Qiang Ma
Zihang Xu
Haibin Liang
Huaifeng Li
Yuanyuan Ye
Shanshan Xiang
Yijian Zhang
Lin Jiang
Yunping Hu
Zheng Wang
Xuefeng Wang
Yong Zhang
Wei Gong
Yingbin Liu
author_facet Fei Zhang
Qiang Ma
Zihang Xu
Haibin Liang
Huaifeng Li
Yuanyuan Ye
Shanshan Xiang
Yijian Zhang
Lin Jiang
Yunping Hu
Zheng Wang
Xuefeng Wang
Yong Zhang
Wei Gong
Yingbin Liu
author_sort Fei Zhang
collection DOAJ
description Abstract 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.
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spelling doaj.art-accbded771ea4901b1c0c3295112da5f2022-12-21T23:59:27ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662017-05-0136111110.1186/s13046-017-0531-3Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancerFei Zhang0Qiang Ma1Zihang Xu2Haibin Liang3Huaifeng Li4Yuanyuan Ye5Shanshan Xiang6Yijian Zhang7Lin Jiang8Yunping Hu9Zheng Wang10Xuefeng Wang11Yong Zhang12Wei Gong13Yingbin Liu14Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineLaboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13046-017-0531-3MetastasisInvasionGallbladder cancerTCTPDihydroartemisinin
spellingShingle Fei Zhang
Qiang Ma
Zihang Xu
Haibin Liang
Huaifeng Li
Yuanyuan Ye
Shanshan Xiang
Yijian Zhang
Lin Jiang
Yunping Hu
Zheng Wang
Xuefeng Wang
Yong Zhang
Wei Gong
Yingbin Liu
Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
Journal of Experimental & Clinical Cancer Research
Metastasis
Invasion
Gallbladder cancer
TCTP
Dihydroartemisinin
title Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
title_full Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
title_fullStr Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
title_full_unstemmed Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
title_short Dihydroartemisinin inhibits TCTP-dependent metastasis in gallbladder cancer
title_sort dihydroartemisinin inhibits tctp dependent metastasis in gallbladder cancer
topic Metastasis
Invasion
Gallbladder cancer
TCTP
Dihydroartemisinin
url http://link.springer.com/article/10.1186/s13046-017-0531-3
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