塞来昔布通过诱导人NAG-1基因表达抑制胃癌生长

Celecoxib Inhibits Gastric Adenocarcinoma Growth via Inducing Expression of Human Nonsteroidal Anti-inflammatory Drug Activated Gene

目的探讨环氧合酶-2(COX-2)抑制剂塞来昔布在人体内抑制胃癌及诱导非甾体类抗炎药物(NSAID)活化基因(NAG-1)的作用。方法36例胃癌患者在接受胃癌根治术或胃大部切除术前随机分为2组。塞来昔布组:20例,术前口服塞来昔布,0.2 g,qd×7 d。对照组:16例,术前不用任何抗肿瘤药物。术中切除标本送组织病理学研究;采用DNA末端原位标记染色法检测胃癌细胞凋亡;免疫组化检测胃癌细胞COX-2表达;半定量RT-PCR技术检测两组胃癌组织NAG-1 mRNA表达。结果塞来昔布组胃癌组织凋亡阳性细胞的积分光密度值高于对照组(180.20±42.67 vs 10.28±5.02,P<0.05),塞来昔布组NAG-1 mRNA(0.22±0.13)也较对照组(0.12±0.08)上调(P<0.05)。两组COX-2蛋白表达率(75.0%vs 87.6%)差异无统计学意义。结论塞来昔布在人体内通过诱导NAG-1基因转录,促进胃癌细胞凋亡。

Objective To investigate the effect of cyclooxygenase2 inhibitor celecoxib on the suppression of human gastric cancer（GC） growth and the induction of nonsteroidal anti-inflammatory drug activated gene（NAG-1） expression.Methods Thirty-six GC patients were randomly divided into two groups before curative surgery.Celecoxib group patients（n =20） took celecoxib orally 0.2 g,qd for 7 days before operation.Control group（n =16） took no medication before resection.The resected specimens were used for histological and pathological study,and apoptosis of tumor cells were evaluated by the terminal deoxynucleotide transferase（TdT）-mediated dUTP nick end-labeling assay（TUNEL）.COX-2 expression was assessed by immunohistochemical staining.Semi-quantitative reverse transcription polymerase chain reaction（RT-PCR） assay was used to measure NAG-1 mRNA expression in GC tissue of both groups.Results Apoptosis IOD score of the GC cells in celecoxib group was significantly higher than that in control group（180.2±42.67 vs 10.28±5.02,P〈0.05）.NAG-1 mRNA expression was higher in celecoxib group（0.22±0.13） than in the control（0.12±0.08,P〈0.05）.There was no significant difference of COX-2 expression rate between both groups（75.0% vs 87.6%, P〉0.05）.Conclusion Celecoxib can enhance apoptosis of GC cell by induction of NAG-1 gene transcription in human.