目的:应用MRMT-1大鼠乳腺癌骨转移性癌痛模型探讨环氧化酶.2选择性抑制剂塞来昔布的抗肿瘤及镇痛作用机制。方法:用MRMT-1大鼠乳腺癌细胞建立的49只大鼠癌痛模型。造模20天后将大鼠随机分为治疗组(25只)与对照组(24只),于塞来昔布干预后第21天取转移性骨肿瘤组织行COX-2、VEGF蛋白表达水平测定及机械性痛觉超敏测量。结果:治疗组转移性骨肿瘤组织中COX-2和VEGF的蛋白表达与对照组比较显著降低(4266.42±733.96VS7731.96±1361.41;6237.05±771.24VS7833.06±1053.66 P〈0.05)。机械性痛觉超敏反应全面减弱,差异有显著性意义(P〈0.05)。结论:塞来昔布可能通过下调COX-2、VEGF水平抑制肿瘤进展并具有良好的镇痛作用。
Objective: To investigate the mechanism of cyclooxygenease-2 (COX-2) specific inhibitor celecoxib on the treatment of cancer pain in rats induced by MRMT-1 mammary gland carcinoma cells. Methods:The rat model of metastatic bone cancer pain was produced by intra-tibial inoculations of MRMT-1 rat mammary gland carcinoma cells in Sprague-Dawley rats. Twenty days after cancer pain model establishment, all 49 rats were randomly divided into control group (24 rats) and celecoxib treatment group (25 rats). Twenty-one days after celecoxib treatment, COX-2 and VEGF protein expression in segments of metastatic bone cancer rats were detected by immunohistochemical SP method, respectively. Mechanical allodynia was measured by von Frey filaments test. Results: The expressions of COX-2 and VEGF proteins in celecoxib treatment group were significantly less than those in control group(4266.42 ±733.96 VS 7731.96 ±1361.41; 6237.05 ±771.24 VS 7833.06 ±1053.66, P 〈0.05). The mechanical allodynia in celeeoxib treatment group was significantly less than that in control group ( P 〈 0. 05 ). Conclusion: Celecoxib was an effective chemotherapeutic agent for inhibiting tumor progression and relieving cancer pain by down-regulation of COX-2 and VEGF expressions in the rat MRMT-1 mammary gland carcinoma cells model.