非甾体类抗炎药塞来昔布对肺腺癌抑制作用的实验研究

Abstract

目的观察选择性环氧合酶-2(COX-2)抑制剂塞来昔布在体内及体外对肺癌细胞的抑制作用.方法噻唑蓝(MTT)比色法检测肺癌细胞的增殖抑制,流式细胞仪检测塞来昔布处理后肺癌细胞周期变化,通过裸鼠移植瘤实验,比较移植瘤重量检测塞来昔布对肺癌细胞体内抑制作用,TUNEL法染色检测移植瘤癌细胞凋亡.结果塞采昔布对肺癌细胞增殖有抑制作用,且呈剂量依赖关系,IC 50为50umol/L.塞来昔布可将细胞阻滞在G0/G1期,阻碍G1期细胞进入S期.称量裸鼠移植肿瘤的瘤结节重量,对照组平均瘤重(2 1567±0.9750)g,药物组平均瘤重(0.9783±0.5423)g,两组有显著性差异(P＜0.05),抑瘤率为54.64%.TUNEL法移植瘤凋亡细胞染色,对照组凋亡指数(AI)为(1.58±0.61),用药组(9.50±2.51),二组有显著性差异(P＜0.05).结论塞来昔布在体内及体外均对肺癌细胞表现出抑制作用,其将细胞周期阻滞在G1期并诱导肿瘤细胞凋亡可能是抑制肺癌细胞增殖的重要机制.

Objective: To observe that celecoxib, a selective inhibitor of cyclooxygenase-2(COX-2),in vitro and in vivo, inhibited proliferation of cell line of lung cancer. Methods: Antiproliferative effect was obtained by MTT assay. Flow cytometry was used to analyze the effect of celecoxib on cell cycle. .Nude mice bearing lung cancer xenografts were administered with celecoxib, and then the weight of implanted tumors was measured. The apoptotic cells in implanted tumors were stained by the terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) technique. Results: There was a does-dependent inhibition of cell proliferation by celecoxib. 1C50 is 50 umol/L. Celecoxib may induce a GO/Gl cell cycle arrest, inhibited the Gl cells to S phrase transition. The average weight of tumor nodules in control group was (2.1567+0.9750)g,while in the experimental group it was (0.9783±0.5423) g, with the inhibitive rate being 54.64%. There is statistical difference (P＜0.05). Apoptosis of transplanted tumor cells showed that apoptotic index (Al) of the control group was (1.58+0.61), while in the experimental group it was (9.50±2.51), showing significant difference (P＜0.05). Conclusions: Celecoxib shows suppressive effect on adenocarcinoma cells of lung. Induction of G0/G1 cell cycle arrest and apoptosis might be its important mechanisms.