ABSTRACT
Cholangiocarcinoma (CCA) is a type of epithelial cancer with poor outcomes and late diagnosis. Accumulating evidence has demonstrated the promoting role of plasminogen activator, urokinase (PLAU) in several tumor types, while its function in CCA is largely unknown. The expression of PLAU in CCA was determined by data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database and further confirmed in human tissues using immunohistochemical (IHC) staining. Moreover, PLAU-silencing CCA cell models were constructed for subsequent functional assays in vitro and in vivo. PLAU expression in CCA was significantly higher than that in normal tissues. High PLAU expression was positively correlated with poor patients' survival. PLAU knockdown remarkably suppressed proliferation and migration of CCA cells, whereas enhanced apoptosis. Consistently, tumor growth in mice injected with PLAU-silencing CCA cells was also impaired. Furthermore, we revealed that the activation of NF-κB signaling was required for PLAU-induced malignant phenotypes of CCA cells. Inhibiting the high expression of PLAU in CCA may be a potential entry point for targeted therapy in CCA patient.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Animals , Mice , NF-kappa B/metabolism , Urokinase-Type Plasminogen Activator/metabolism , Plasminogen Activators/metabolism , Signal Transduction , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/pathology , Bile Ducts, Intrahepatic/metabolism , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Cell Proliferation/genetics , Cell Line, Tumor , Cell Movement/geneticsABSTRACT
PURPOSE: Overexpression of survivin in breast cancer cells is associated with aberrant inhibition of apoptosis which leads to massive proliferation of cancer cells. Downregulation of survivin by the anticancer agent prodigiosin can efficiently induce apoptosis in cancer cells. METHODS: The levels of survivin expression in breast cancer stem like side population (SP) cells were assessed. Analyzed were also the rate of apoptosis, drug resistance and the efficiency of clone formation of breast cancer SP cells after treatment with progiosin. RESULTS: Breast cancer samples contained about 2.7% of cancer stem like SP cells which possessed elevated mRNA expression of stem cell proteins Oct-4, EpCAM and ABC transporter ABCG2, essential for the maintenance of SP cells. Furthermore, the SP cells displayed overexpression of survivin in conjunction with reduced apoptosis and increased multidrug resistance. After treatment with prodigiosin, the SP cells became more sensitive to apoptosis and to several chemotherapeutic agents. CONCLUSION: These data suggest that increased expression of survivin in SP cells is one of the major factors involved in apoptosis and resistance to chemotherapy.
Subject(s)
Apoptosis , Breast Neoplasms/pathology , Inhibitor of Apoptosis Proteins/physiology , Neoplastic Stem Cells/pathology , Adult , Aged , Breast Neoplasms/drug therapy , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , SurvivinABSTRACT
A 74-year-old woman presented with a one-week history of persistent cough. A chest x-ray and computed tomography images revealed features mimicking lung cancer, which included a large solitary consolidation and hilar lymphadenopathy. She had received low-dose amiodarone (200 mg/day) for treatment of atrial fibrillation for more than 2.5 years. The tumour-like abnormalities did not disappear until the discontinuation of amiodarone therapy. The finding of low-dose amiodarone causing tumour-like abnormalities on a chest x-ray is unique. Once amiodarone-induced tumour-like changes are diagnosed, therapeutic options are limited. In most cases, the tumour-like changes are reversible, if diagnosed early. An unusual case involving amiodarone-induced pulmonary abnormalities is reported, followed by a review of the relevant literature.