奥曲肽联合NSAIDs对结肠癌细胞生长的影响及作用机制

目的研究奥曲肽与非甾体类抗炎药物(NSAIDs)塞来昔布联合用药对人结肠癌细胞生长的影响及作用机制。方法 CCK-8法测定塞来昔布、奥曲肽单用及两者联合应用对人结肠癌细胞SW480增殖的影响;流式细胞技术检测细胞周期变化及细胞凋亡率的变化;Western blot检测未折叠蛋白反应(UPR)的标志分子BiP蛋白的表达。结果奥曲肽与塞来昔布联合应用与各自单用相比,细胞增殖减少,凋亡增加(P<0.05),各细胞时相的比例G2M期无明显变化(P>0.05),G0G1期增加(P<0.05),S期减少(P<0.05)。0、20、40、60、80μmol/L塞来昔布作用后细胞BiP表达量逐渐增加,80μmol/L塞来昔布与0、0.25、0.5、1、2mg/L奥曲肽作用后细胞BiP的表达量均减少。结论奥曲肽与塞来昔布联合应用能增强塞来昔布的抗肿瘤作用,其作用机制与奥曲肽抑制塞来昔布引起的UPR相关。

Effect of Octreotide Combined with NSAIDs on Growth of Colon Cancer Cells and Action Mechanism

Objective To study the effect of octreotide combined with celecoxib on growth of colon cancer cells and the action mechanism.Methods Human colon cancer SW480 cells were treated with celecoxib and octreotide alone or in combination.The cell proliferation was examined by the method of CCK-8.The cell cycle and apoptosis rate were analyzed by flow cytometry.Western blot was used to detect the level of BiP expression.Results As compared with octreotide and celecoxib alone,cell proliferation was reduced,apoptosis rate increased(P<0.05),the proportion of cells in G2M phase had no significant change(P>0.05),that in G0G1 phase was increased(P<0.05),and that in S phase was decreased in octreotide in combination with celecoxib group(P<0.05).At the concentration of celecoxib being 0,20,40,60 and 80 μmol/L,BIP expression was gradually increased.The combined use of 80 μmol/L celecoxib combined with octreotide(0,0.25,0.5,1.0,and 2.0 mg/L respectively) could reduce the BiP expression.Conclusion Octreotide in combination with celecoxib can enhance the effect of antitumor,which might be significantly correlated with the inhibition of celecoxib-induced UPR.