生长抑素类似物抑制胆管癌细胞增殖的研究

目的探讨生长抑素类似物奥曲肽(OCT)对人胆管癌细胞细胞株QBC939的抑制作用及可能的作用机制。方法四氮唑蓝(MTT)法检测OCT对人胆管癌细胞株QBC939增殖的影响,流式细胞仪检测OCT对细胞周期变化的作用,免疫组织化学法研究OCT对人胆管癌细胞株QBC939P27KIP1蛋白表达变化的影响。建立胆管癌裸鼠模型,进一步探讨生长抑素的作用。结果MTT法检测不同浓度OCT(5、0.5、0.05、0.005mg/L)作用于QBC93948h后,实验组0.5、5mg/L组和对照组吸光度(A)值比较差异有统计学意义(P<0.05)。细胞生长率分别为83.80%,80.28%,77.53%,65.32%。流式细胞仪分析显示不同浓度OCT作用于QBC93948h后,G0/G1期细胞明显增多(P<0.05)。免疫组织化学P27KIP1蛋白表达随OCT浓度的增加而增强(P<0.05)。建立胆管癌裸鼠模型后,OCT干预21d后实验组瘤重明显小于对照组(P<0.05)。结论OCT可抑制人胆管癌细胞的增殖。在一定范围内呈剂量依赖性,其抗肿瘤作用机制主要是通过细胞周期阻滞来实现的,而这一作用的实现可能与P27KIP1蛋白表达的上调有关。

Octreotide,a somatostatin analogue,inhibits the growth of cholangiocarcinoma cells

Objective To investigate the possible mechanism underlying in-vivo and in-vitro growth inhibition of cholangiocarcinoma cell line QBC939 by octreotide(OCT),a somatostatin analogue.Methods Cholangiocarcinoma cell line QBC939 were cultured in vitro.MTT assay were used to determine the antiproliferative effect of different OCT doses on QBC939 cell growth rate.Changes in QBC939 cell cycle after OCT administration were evaluated by flow cytometry.The effects of OCT on the expression of P27KIP1 were evaluated by immunochemistry.Nude mouse models of tumor heterograft were established and used for further evaluation of OCT antiproliferative effects.Results MTT assay showed that OCT significantly reduced QBC939 cell growth in a dose-dependent pattern.After treated with 0.005～5 mg/L OCT for 48 hours,the cell growth rates were 83.8%,80.28%,77.53% and 65.32%,respectively.Between control group and experimental groups,the A values were significantly different(P<0.01).Results of flow cytometry suggested that OCT accounted for increased arrest of cell cycle in G0/G1 phase(P<0.05).Expression of P27KIP1 was dose-dependently enhanced with octreotide treatment.The weights of QBC939 xenografts in OCT-treated group were lower than those in the control group.Conclusion OCT appeared to inhibit the growth of human extrahepatic cholangiocarcinoma cell line QBC939 at least partly in a dose-dependent pattern.Cell cycle arrest underlying such effects may be correlated with the up-regulation of P27KIP1.