消化道肿瘤环氧合酶-2表达与凋亡抑制蛋白及化疗药敏性的关系

目的 探讨消化道肿瘤环氧合酶(COX)-2表达与凋亡抑制蛋白及体外化疗药敏性的关系.方法 对84例胃癌、大肠癌标本进行噻唑蓝(MTT)比色法体外化疗药物敏感性实验,并进行COX-2、p53、Survivin、bel-2免疫组织化学染色.结果 肿瘤组织COX-2、p53、Survivin、bel-2表达率分别为70.3%、64.3%、89.3%、60.7%;COX-2与Survivin、bcl-2表达呈正相关(r=0.5072、0.3783,均P<0.01).在肿瘤COX-2强表达组,紫杉醇(PTX)、表阿霉素(eADM)、羟基喜树碱(OPT)对肿瘤细胞抑制率明显低于弱表达组(均P<0.05);p53强表达与PTX、顺铂(DDP)对肿瘤细胞的抑制率明显降低有关(均P<0.05);Survivin强表达时,长春新碱(VCR)、DDP对肿瘤细胞抑制率明显降低(均P<0.05);bcl-2强表达时,5-氟尿嘧啶(5-Fu)、VCR、eADM、奥沙利铂(OXA)对肿瘤细胞抑制率明显低于弱表达组(均P<0.05).结论 消化道肿瘤COX-2通过抑制肿瘤细胞凋亡参与了肿瘤的多药耐药.

Relationship between the expression of cyclooxygenase-2, inhibitor of apoptosis proteins and chemosensitivities in gastrointestinal carcinomas

Objective To investigate the re'ationship between the expression of cyclooxygenase-2 (COX-2), inhibitor of apoptosis proteins (IAPs, including p53, Survivin, bcl-2) and chemosensitivities in gastrointestinal carcinomas. Methods The expression of COX-2 ,p53, Survivin and bcl-2 was detected immunohistochemically, and the chemosenisitivities of 9 drugs was measured by MTT assay in 84 tissue specimens of gastrointestinal carcinomas. Results The positive expression rate of COX-2, p53, Survivin and bcl-2 was 70.3% ,64. 3% ,89. 3% and 60.7% respectively. There was a significant correlation between the expression of COX-2 and Survivin, and COX-2 and bcl-2 (r=0. 5072,0. 3783, both P<0. 01). In terms of relationship between the expression of four MDR-related factors and inhibition rate of tumor cells, the inhibition rate for PTX,eADM and OPT in COX-2 strong expression group was lower than that in weak group (all P<0.05). The inhibition rate to PTX and DDP was significantly lower in the p53 strong expression group than in the weak group (both P<0.05). When Survivin was expressed strongly,the inhibition rate for VCR and DDP was reduced significantly (both P<0.05). There was the lower inhibition rate for 5-Fu,VCR,eADM and OXA in bcl-2 strong expression group (all P<0. 05). Conclusion COX-2 could participate in MDR of gastrointestinal carcinomas by inhibiting the apoptosis of tumor cells.