环氧合酶-2选择性抑制剂塞莱昔布调节胃癌细胞多药耐药性的实验研究

 目的 观测环氧合酶-2（COX-2）抑制剂塞莱昔布（Celecoxib）对多药耐药细胞株SGC7901／VCR多药耐药（MDR）的逆转及P-糖蛋白（P-gp）的调变作用，探讨COX-2对胃癌细胞MDR调节作用。方法 以长春新碱（VCR）诱导的人胃癌多药耐药细胞SGC7901／VCR为研究对象，应用流式细胞术、MTT法及免疫细胞化学方法研究COX-2抑制剂塞莱昔布对耐药性的逆转作用及对P-gp的调变作用。结果 MTT显示塞莱昔布明显抑制SGC7901、SGC7901／VCR细胞的生长，并呈时间、剂量依赖性。经非细胞毒剂量（2.5 μmol／L）的塞莱昔布作用后，SGC7901／VCR细胞的多药耐药性得到部分逆转，表现为靶细胞对多种化疗药物的敏感性显著增加，逆转倍数为1.09 ~ 6.28；流式细胞仪分析发现，塞莱昔布介导的SGC7901／VCR细胞耐药性的逆转伴有胞内多柔比星浓度的升高；免疫细胞化学研究显示，经塞莱昔布作用后耐药株SGC7901／VCR表达P-gp强度下降。结论 塞莱昔布能有效地抑制肿瘤细胞的生长，且部分逆转SGC7901／VCR细胞的多药耐药性，其可能主要通过影响P-gp的药物泵功能实现。

Reversing effects of cyclooxygenase-2 inhibitor celecoxib on multi-drug resistance of SGC7901/VCR gastric carcinoma line

Objective To study the activity of COX-2 inhibitor Celecoxib partial reversing effect upon multidrug-resistant (MDR) of cancer and its effect on the expression of P-glycoprotein. To indicate the role of COX-2 take part in mediation of MDR in gastric carcinoma. Method Taking human gastric cancer cell line resistant to vincristine (SGC7901/VCR) as targets to investigate COX-2 inhibitor Celecoxib Partial reversing effect on multidrug resistance and mechanism was measured by flow cytometry, MTT and immuno－histochemistry. Results MTT analyzed that celecoxib was able to inhibit the growth of SGC7901, SGC7901/VCR cells in a dose-and time-dependent manner in vitro; After exposure of SGC7901/VCR cells with non-cytotoxic dose of celecoxib (2.5 umol/l), the sensitivity of target cells to chemotherapeutical agents was re－markably increased, indicating that the MDR of SGC7901/VCR cells was partly reversed. The reversal times varied from 1.09 to 6.28; With the help of flowcytometry. We found increase of intracellular concentration of adriamycin in SGC7901/VCR cells during celecoxib mediated reverse of MDR. Immunocytohistochemistry showed over-expression of P-glycoprotein in SGC7901/VCR cells was decreased after exposure to the cele－coxib. Conclusions Celecoxib was able to significantly inhibit the growth of tumor cells, and it can partly reverse MDR of SGC7901/VCR cells through interfering the P-glycoprotein expressions.