塞来昔布对肺癌的抑制作用机制研究  

Studies on the inhibitory effects of Celecoxib on lung carcinoma

作　　者：蒋莉 蒋艳[2,3,4] 

机构地区：[1]湖南省武冈市人民医院,湖南武冈422400 [2]南华大学附属第一医院,湖南衡阳421001 [3]南华大学 [4]南华大学药物药理研究所,湖南衡阳421001

出　　处：《肿瘤药学》2011年第3期216-219,共4页Anti-Tumor Pharmacy

摘　　要：目的探讨环氧化酶抑制剂(COX-2)抑制剂塞来昔布对于A549肺癌细胞增殖及其小鼠移植瘤生长的抑制作用及可能机制。方法加不同浓度塞来昔布与A549肺癌细胞共培养,MTT法检测细胞增殖,流式细胞仪法检测细胞凋亡情况。A549细胞移植入BALB/c裸小鼠皮下后,随机分为实验组和对照组,实验组隔日腹腔注射塞来昔布30mg·kg-1,对照组隔日腹腔注射等体积生理盐水,24d后处死移植瘤小鼠,计算抑瘤率,RT-PCR检测移植瘤组织中COX-2和VEGFmRNA表达水平,同时酶联免疫检测小鼠血清中MMP-9浓度,免疫组化检测瘤组织中微血管密度(MVD)。结果塞来昔布在体外对细胞株A549的生长抑制作用呈剂量、时间依赖性,且经塞来昔布作用后,A549细胞G0/G1期比例增加,S、G2/M期比例下降。在体实验显示,塞来昔布具有明显的抑制A549肺癌移植瘤增殖的作用,同时能抑制移植瘤组织中COX-2、VEGF表达,降低血清MMP-9浓度,减少移植瘤中微血管密度(P<0.05)。结论塞来昔布在体内外均可显著抑制A549肺癌细胞的增殖,而诱导肿瘤细胞凋亡,抑制肿瘤血管生成和降低癌细胞侵袭能力是其可能的作用机制。Objective To investigate the inhibitory effects of Celecoxib, a selective COX-2 inhibitor, on the proliferation of A549 lung carcinoma cell and growth of transplanted A549 lung carcinoma in micein, as well as the possible mechanism. Method The proliferation and cell apoptosis of A549 lung carcinoma cells was measured by MTI7 assay and flow cytometric analysis. BALB/c mice receiving tumor implantation were randomly divided into control （0.9% NaC1） and Celebrex （30 mg/kg） group. On the 24th day, all the mice were killed. The expressions of VEGF and COX-2 in xenografted tumor tissue were analyzed by RT- PCR, MMP-9 by ELISA, and MVD by immunohistochemical staining. Results Celecoxib could inhibit the proliferation of A549 cell by a time-and dose-dependent manner. Celecoxib can increase the percent- age of cell in G0/G1 and decrease that in S and G2/M. Celebrex inhibited the growth of transplanted A549 lung carcinomain vitmsignificantly. And the COX-2, VEGF mRNA expression level in transplanted car- cinoma tissue, MMP-9 expresion level in serum, and MVP in tissue was significantly down-regulated after the treatment with Celebrex （P〈0.05）. Conclusion Celebrex could inhibit A549 lung cancer cells prolif- eration in vitro an in vivo. Induction of apoptosis and antiangiogenesis and inhibition of migration might be the mechanism by which celecoxib exerts its chemopreventive and therapeutic effects.

关 键 词：肺癌 塞来昔布 血管内皮生长因子 MPP 环氧化酶-2抑制剂 

分 类 号：R979[医药卫生—药品]