Abstract
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.
Highlights
Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis
We found that the translationally controlled tumor protein (TCTP) protein was aberrantly expressed in Gallbladder cancer (GBC) and that its expression was correlated with metastasis and poor prognoses in GBC patients
TCTP is associated with gallbladder cancer metastasis To determine the role of TCTP in GBC progression, we used IHC to detect TCTP expression levels in 73 GBC specimens and 103 cholecystitis tissues
Summary
Patients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer. Gallbladder cancer (GBC) is the most malignant type of biliary tract cancer. It is the seventh most common gastrointestinal cancer, with an incidence of 2.5 per 100,000 persons [1,2,3]. New therapeutic approaches that target the key proteins that mediate metastasis are urgently needed to treat this aggressive tumor. Blocking metastasis should be considered one arm of therapeutic strategies aimed at treating GBC, even in the absence of detectable metastatic lesions
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