Objective To investigate the effects of β2-adrenergic antagonist ICI118 ,551 on pancreatic cancer cell G1/S phase arrest and its action mechanism .Methods The cell cycle indexes were determined by the flow cytometry assay ;the expressions of Cyclin D1 and Cyclin E were analyzed by Western blot ;the activation of NF-κB was measured by electrophoretic mobility shift assay ;the proliferation of PanCa cells was determined by BALB/c athymic nude mice subrenal capsular assay .Results β2-adrenergic antagonist ICI118 ,551 significantly induced G1/S phase arrest compared with β1-adrenergic antagonist metoprolol in MIA PaCa-2 and BxPC-3 cell lines .ICI118 ,551 inhibited the expressions of Cyclin D1 and Cyclin E and reduced the activation of NF-κB .The proliferation of PanCa cells was strongly suppressed in the renal capsule xenografts in mice after ICI 118 ,551 treatment .Conclusion The blockage ofβ2-adrenoceptor markedly induces PanCa cells to arrest at G1/S phase and inhibits the proliferation of pancreatic cancer cells .%目的 研究β2受体阻滞剂ICI118,551诱导胰腺癌细胞G1/S期阻滞及其相关机制.方法 应用β2受体阻滞剂ICI118,551和β1受体阻滞剂美托洛尔干预胰腺癌细胞,通过流式细胞仪检测细胞周期、Western blot技术检测β2受体阻滞剂对细胞周期调节蛋白Cyclin D1和Cyclin E表达的影响,EMSA技术检测核转录因子NF-κB的活性,构建裸鼠肾包膜下移植瘤模型检测肿瘤增殖情况.结果 ICI118,551可显著诱导胰腺癌细胞G1/S期阻滞,并显著优于美托洛尔组(P<0.05);ICI118,551干预组抑制Cyclin D1和Cyclin E的表达,并可抑制NF-κB的活性;裸鼠肾包膜下移植瘤实验显示ICI118,551可显著抑制胰腺癌细胞的增殖.结论 β2受体阻滞剂ICI118,551可有效诱导胰腺癌细胞G1/S期阻滞,抑制胰腺癌细胞的增殖.
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