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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Apoptosis, Biomarkers, Tumor, Cell Line, Tumor, Cell Movement, Cell Proliferation, Deoxycytidine, Epithelial-Mesenchymal Transition, Histamine Agonists, Histamine H3 Antagonists, Humans, Imidazoles, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Pancreatic Neoplasms, Receptors, G-Protein-Coupled, Receptors, Histamine, Receptors, Histamine H4, Thiourea, Tumor Burden, Xenograft Model Antitumor Assays.
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Does clobenpropit enhance anti-tumor effect of gemcitabine in pancreatic cancer? Context: To evaluate the anti-tumor effect of clobenpropit, which is a specific H3 antagonist and H4 agonist, in combination with gemcitabine in a pancreatic cancer cell line. Three kinds of human pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and AsPC-1) were used in this study. Expression of H3 and H4 receptors in pancreatic cancer cells was identified with Western blotting. Effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. Alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. An in vivo study with a Panc-1 xenograft mouse model was also performed. H4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of H3 receptor. Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated E-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction. Also, clobenpropit inhibited tumor growth (gemcitabine 294 ± 46 mg vs combination 154 ± 54 mg, P = 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5%, gemcitabine 25.8%, clobenpropit 9.7% and combination 40.9%, P = 0.001) by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse.
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Clobenpropit enhanced the anti-tumor effect of gemcitabine in pancreatic cancer cells through inhibition of the epithelial-mesenchymal transition process. Final Decision: yes