特异性环氧合酶-2抑制剂与不同抗癌药联用对胶质瘤细胞生长的影响

Antitumor effects of specific cyclooxygenase-2 inhibitors combined with chemotherapeutic agents on glioma cells in vitro

目的 观察特异性环氧合酶-2抑制剂依托昔布和塞来昔布（celebrex）与长春新碱（VCR）、顺铂（DDP）、鬼臼噻吩甙（VM-26）等抗癌药联用对胶质瘤细胞增殖的影响。方法30μmol／L依托昔布、100μmol／L塞来昔布与不同浓度的VCR、DDP、VM-26单用、联用48h。噻唑蓝（MTT）比色法检测各组抑制率，中效原理和金正均法评价特异性环氧合酶-2抑制剂与各抗癌药联用的效果。结果30μmol／L依托昔布和100μmol／L塞来昔布单用对胶质瘤细胞增殖抑制率分别为（40．87±1．88）％和（46．81±2．37）％；不同浓度（1、10、100mg／L）的VCR、DDP、VM-26单用对胶质瘤细胞增殖均有不同程度的抑制作用；依托昔布和塞来昔布与不同浓度VCR、DDP、VM-26联用组的抑制率均高于各药物单用组，具有协同作用。结论依托昔布和塞来昔布与抗癌药联用后起协同作用，特异性环氧合酶-2抑制剂可作为抗癌药的化疗增敏剂。

Objective To study the effects of two specific cyclooxygenase-2 inhibitors, etocoxib and celeeoxib, combined with chemotherapeutic drugs vincristine （VCR）, diamminedichloroplatinum （DDP） and vumon （VP-26） on glioma cell line U251,and to evaluate whether the specific eyelooxygenase-2 inhibitors can he used as a synergetic agent in glioma chemotherapy. Methods The human glioma cell line U251 MG was eutured for 48 h with etocoxib and celecoxib, VCR, DDP or VP-26 alone, or in conbination with etocoxib/celecoxib and gradient concentrations （ 1,10,100mg/L） of VCR, DDP, and VM- 26, respectively. MTT assay was performed to detect the cells proliferation. Median-effect principle and Professor Jin＇ s evaluation methods were applied to evaluate the interaction between the specific cyclooxygenase-2 inhibitors and chemotherapeutic agents. Results The growth inhibition rate of U251 MG cells was （40.87± 1.88）% and （46.81 ±2.37）% after treatment with 30μmol/L etocoxib and 100 μmol/L celecoxib,respectively. The inhibition rate of U251 MG cells treated with VCR, DDP and VP-26 at different concentrations （ 1,10, or 100μmol/L） was （39.83±1. 14）%, （45.90 ± 1.27）%, （73.47 ± 3.0）% ;（38.20± 1.65）%, （49.37 ± 1.48）%, （87.52 ± 4.00）% ; （42.84± 2.43）%, （53.48 ±2.67 %, （ 88.56±2.40） %, respectively. The inhibition rate was relatively higher in the cells treated by the two specific cyelooxygenase inhibitors and the chemotherapeutic agents at different concentrations （P 〈 0.05 ） ,and a synergetie effect existed. Conclusion Both etoeoxib and celecoxib suppress human glioma cells in vitro and exert a synergetic role when combined with different concentrations of VCR, DDP, or VM- 26 ,indicating that the two cyclooxygenase inhibitors may be used as a chemotherapeutic sensitizer for chemotherapy of human gliomas.