| Pancreatic cancer is a kind of malignant tumor with the clinical onset concealment, the rapid development and poor prognosis. By the influence of the anatomical relation of the pancreas and surrounding tissues and organs, it often happens surrounding tissues, organs infringed and distant metastasis. Because there are no apparent specific symptoms and signs at the early period, and the lack of a reliable early diagnostic methods, at time of diagnosis of more advanced, the prognosis is poor, about 83 percent of patients die within 1 year. Now the early surgical resection is supposed to the only method of cure for pancreatic cancer, but Upon diagnosis, 85 percent of patients with pancreatic cancer already were advanced stage or distant metastasis, surgical resection only 10%-15%, therefore in pancreatic cancer chemotherapy in comprehensive treatment still holds the important position, and it is necessary to explore new drugs to improve outcomes.Quinolone compounds are used as clinically antibacterial agents. which function in bacterial DNA gyrase. these drugs act in bacterial DNA gyrase to prevent germs multiply and kill bacteria by inhibiting bacterial DNA copy, transcription and damage its repair process.clinical application effect of Quinolone is very good. Because the sequence of tyrosine active site is homology, between the topologicalⅡof eukaryotic cells with the bacterial DNA gyrase and both catalytic functions are similar. so people expect to synthesise the new quinolone antitumor drugs through the structure transformation which can inhibit mammals activity of topologicalⅡ.The study use acetobromoglucose replace C-3 carboxyl of fluoroquinolone synthetic ofloxacin C-3 acylhydrazone derivatives and explores pancreatic cancer BxPc-3 cell proliferation inhibiting and apoptosis promoting role of this compounds in order to screen candidates drug of the treatment of pancreatic cancer for the further development and utilization of provide experimental basis.Objective: 13 categories of Quinolone derivatives as candidate agents was screened for finding the compounds which have high inhibiting activity to proliferation of BxPc-3 cells, and studied the antineoplastic mechanism of the compounds,in order to provide references for the development of new anticancer drugs.Methods: The proliferation of the cells and the inhibition effect of Quinolone derivatives on the cell proliferation were examined by MTT assay. Cell apoptosis was observed by fluorescence microscope techniques with Hoechst 33258 associated with propidium iodide (PI) staining and TUNEL assay. DNA ladder was observed through agarose gel electrophoresis. Western blotting was used to assay changes of the proteins correlated cell apoptosis.Results: The results of drug screening indicated thatFQ4and FQ16 possessed high inhibiting activity to proliferation of BxPc-3 cells. The cell proliferation was inhibited by FQ16 at 0.625μmol·L-1~10μmol·L-1 in dose and time dependent manners. The approximate the concentration of 50% growth inhibition (IC50) values of FQ16 for 24h was 4.00μmol·L-1. More apoptotic cells were observed in FQ16 treated the cells for 24h at the range of concentration from 2.80μmol·L-1 to6.37μmol·L-1compared to the controls by TUNEL assay, the difference was statistically significant and the typical ladder DNA in apoptotic cells were detected by agarose gel electrophoresis. Treatment of BxPc-3 cells with different FQ16 concentration for 24 hours increased the protein expression of caspase-3, caspase-9, caspase-8, bax, and p53, induced cytosolic accumulation of activities caspase-9 and caspase-8, whereas protein expression of Bcl-2 was decreased compared with the control group. the protein quantity of cytolymph Cytochrome c decreased and mitochondria Cytochrome c increased. Conclusions1. FQ16 possess high inhibiting activity to proliferation of pancreatic cancer BxPc-3 cells. The cell proliferation is inhibited by FQ16 in dose and time dependent manners.2. FQ16 can induce apoptosis of human pancreatic cancer BxPc-3 cells by mitochondrial- dependent pathways...
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