罗非昔布对胃癌细胞BGC-823内在耐药的逆转作用  

Effects of a specific cyclooxygenase inhibitor Rofecoxib on reversing intrinsic drug resistance of gastric cancer BGC-823

作　　者：朱风尚[1] 陈锡美[1] 王毅军[1] 张霞[1] 

机构地区：[1]同济大学附属同济医院消化科,上海200065

出　　处：《同济大学学报（医学版）》2007年第4期25-28,33,共5页Journal of Tongji University(Medical Science)

摘　　要：目的探讨罗非昔布和抗癌药5-氟尿嘧啶(5-FU)、顺铂(DDP)和依托泊甙(VP-16)联用抗胃癌细胞株BGC-823的疗效及多药耐药(multidrug resistance gene,MDR)相关基因上的机制。方法0.1μmol/L罗非昔布单用和与不同浓度梯度化疗药5-FU、DDP及VP-16联合应用于胃癌细胞株BGC-823 48 h,MTT法检测各自的抑制率,中效原理评价用药的协同作用;以0.1μmol/L、1.0μmol/L和10μmol/L罗非昔布干预胃癌细胞48 h,RT-PCR观察用药前后多药耐药相关基因变化情况。结果抗癌药与罗非昔布联用同罗非昔布单用或抗癌药单用比较,联合治疗组协同作用明显(均P<0.01)。RT-PCR显示,胃癌细胞株BGC-823多药耐药相关蛋白(multidrug-associatedprotein,MRP)和谷光甘肽-S-转移酶π(glutathione-S-transferasesπ,GST-π)基因表达,无MDR1表达;罗非昔布干预以后,MRP和GST-π均有不同程度的下降(均P<0.05)。结论罗非昔布可协同抗癌药抗胃癌细胞BGC-823。其协同抗癌机制为逆转或部分逆转MDR现象,是较好的化疗增敏剂。Objective To study the effect of a specific cyclooxygenase inhibitor Rofecoxib combined with chemotherapy drugs including concentration gradient of 5-FU,DDP and VP-16 （ 1 μg/ml, 10 μg/ml and 100 μg/ml） on gastric cancer cell line BGC-823, and to investigate the expression of multidrug resistance gene （MDR） in gastric cancer cell line BGC：823 and the reversal effect of Rofecoxib on intrinsic drug resistance. Methods MTT working solution was added to each culture and calculated the survival rates of gastric cancer cells. Middle effects principle was taken to detect the interaction between the specific cyclooxygenase inhibitor and the chemotherapeutic agents. The expressions and changes of MDR gene family were assessed by reverse transcription-polymerase chain reaction（RT-PCR）. Results Compared with the single agent group, combined groups reached the higher inhibitory rates （P 〈 0.01 ）. MDR gene family was detected on gastric cancer cell line BGC-823; the positive expressions were multidrug-associated protein （MRP） and glutathione-S-transferases π （GST-π） gene, but MDR1 gene was undetectable. After treatment with Rofecoxib （concentration range of 0.1-10 μmol/L）, a significant down regulation of MRP and GST-π mRNA were observed （ P 〈 0.05 ）. Conehtsion Rofecoxib plays a synergetic anti-tumor role in chemotherapy drugs on gastric cancer cell line BGC-823, and which can be partly explained by reversing the intrinsic multidrug resistance associated with genes MRP and GST-π.

关 键 词：胃肿瘤 环氧合酶抑制剂 逆转录多聚酶链反应 多药耐药 

分 类 号：R735.2[医药卫生—肿瘤]