塞来昔布术前干预对人胃癌组织E钙粘蛋白表达的影响

Short-term preoperative treatment of celecoxib,a selective cyclooxygenase-2 inhibitor,on E-cadherin expression in gastric carcinoma tissues

背景与目的:近年来非细胞毒性药物在肿瘤治疗研究中受到关注,研究表明环氧合酶2(Cyclooxygenase-2,COX-2)抑制剂对消化道恶性肿瘤具有显著的抑制作用,本研究观察COX-2抑制剂塞来昔布对人胃癌E钙粘蛋白(E-cadherin)表达的影响,探讨其作用机制。方法:59例胃癌患者随机分为用药组37例,术前每天口服塞来昔布2次,每次200mg,共6d;手术组22例,单纯手术治疗。组织COX-2和E-cadherin表达采用免疫组化检测,术前、术后血清可溶性E-cadherin浓度测定采用酶联免疫吸附试验(ELISA)法。以20名健康人作为正常对照。结果:手术组胃癌组织COX-2阳性率显著高于用药组(P<0.05),而E-cadherin阳性率显著低于用药组(P<0.05)。术前胃癌患者(手术组和用药组)的血清可溶性E-cadherin浓度[(53.47±9.62)ng/mL和(51.57±9.79)ng/mL]显著高于正常对照组[(37.17±5.38)ng/mL](均P<0.01);术后胃癌患者(手术组和用药组)的血清可溶性E-cadherin浓度[(39.29±7.72)ng/mL和(29.29±8.28)ng/mL]较术前显著下降(P<0.01);至第6天时,用药组的血清可溶性E-cadherin浓度[(44.11±8.36)ng/mL]较用药前显著下降(P<0.01)。结论:术前短期使用塞来昔布后术后胃癌组织E-cadherin表达较单纯手术胃癌组织增加。

Background and Objective： Cyclooxygenase-2 （COX-2） inhibitors have been shown to exert chemopreventive effects against gastrointestinal carcinomas. This study was to investigate the effect of celecoxib, a selective COX-2 inhibitor, on the expression of E-cadherin and serum levels of soluble E-cadherin in gastric carcinomas. Methods： Fiftynine gastric carcinoma patients were randomly divided into two groups. surgery group （n=22） and celecoxib plus surgery group （n=37）. Patients in the surgery group underwent surgical resection after diagnosis, while patients in the celecoxib plus surgery group received oral celecoxib, 200 mg twice daily for six days before curative resection. Twenty healthy subjects were recruited as normal controls. COX-2 and E-cadherin expressions were detected by immunohistochemistry. Serum levels of soluble E-cadherin were quantitatively measured using a commercially available enzyme-linked immunosorbent assay （ELISA） kit. Results, Compared to the surgery group, the expression of COX-2 was significantly lower while that of Ecadherin was significantly higher in celecoxib plus surgery group. The concentrations of serum soluble E-cadherin before treatment were significantly higher in the surgery [（53.47±9.62）ng/mL] and the celecoxib plus surgery [（51.57±9.79）ng/mL] groups than in the control group [（37.17±5.38） ng/ml] （P〈0.01）. The soluble E-cadherin levels after surgery in both groups [ （39.29±7.72）ng/mL and （29.29±8.28）ng/mL] were significantly lower than those before surgery （P〈0.01）. The soluble E-cadherin level on the sixth day [（44.11 ±8.36）ng/mL] was significantly lower than that before treatment in the celecoxib plus surgery group （P〈0.01）. Conclusion. Short-term preoperative treatment of celecoxib up-regulates the expression of E-cadherin in gastric carcinomas.