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AIM:To investigate whether octreotide can inhibit thegrowth of human gallbladder cancer cells in vitro and toelucidate the antineoplastic mechanism of octreotide ingallbladder cancer.METHODS:A human gallbladder cancer cell line,GBC-SD,was cultured in vitro.The antiproliferative effects of octreotidewere examined by means of an MTT assay and a colony formingability assay.Morphological variation was investigated underscanning electron microscopy and transmission electronmicroscopy.Cell cycle analysis and apoptosis rate wasevaluated by flow cytometry (FCM) after staining bypropidium iodide.DNA fragmentation was assayed byagarose gel electrophoresis.Immunohistochemical stainingwas performed to evaluate the expressions of mutant-typep53 and bc1-2.RESULTS:The growth curve and colony forming abilityassay showed significant inhibition of octreotide to theproliferation of GBC-SD cells in culture in a time-and dose-dependent manner.After exposure to octreotide,GBC-SDcells showed typically apoptotic characteristics,includingmorphological changes of chromatin condensation,vacuolardegeneration,nucleus fragmentation and apoptotic bodyformation.In FCM profile apoptotic cells showed increasedsub-G_1 peaks in the octreotide group,significantly higherthan the control group (P=0.013).There was also anaugmentation in the cell proportion of G_0/G_1 phase(P=0.015),while the proportion of S phase and G_2/M phaseremained unchanged (P=0.057 and P=0.280,respectively).DNA agarose gel electrophoresis displayed a ladder afterexposure to 1000 nmol/L octreotide.After being treatedwith octreotide,the expressions of both mutant-type p53and bc1-2 decreased considering the percentage of positivecells (P<0.05).CONCLUSION:Octreotide has a negative action to theproliferation of GBC-SD cells,and the mechanism may berelated to cytostatic and cytotoxic effects.The reduction ofmutant-type p53 and bc1-2 expressions may be associatedwith the apoptosis induced by octreotide.
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