常见化疗药物对免疫酶促反应的干扰效应

Interfering effects of common chemotherapeutic drugs on immunoenzymatic reaction system

目的:探讨常见化疗药物对标记酶免疫分析技术的影响。方法:将干扰药物烷化剂(环磷酰胺),抗代谢药(阿糖胞苷、氟尿嘧啶、吉西他滨、地西他滨),抗肿瘤抗生素(依托泊苷),抗肿瘤植物成分药(长春新碱、紫杉醇、多西他赛),其他抗肿瘤药(顺铂、奥沙利铂、卡铂、奈达铂、伊立替康),抗肿瘤靶向药(硼替佐米、郝赛汀、培美曲塞二钠)分别加入辣根过氧化物酶(HRP)+四甲基联苯胺(TMB)反应体系中,用酶标仪测光密度值;同时加入碱性磷酸酶(ALP)+3-(2′-螺旋金刚烷)-4-甲氧基-4-(3″-磷酰氧基)苯-1,2-二氧杂环丁烷(AMPPD)反应体系中,用化学发光仪测相对发光强度值。结果:在HRP酶标反应体系中,与对照组相比,吉西他滨、硼替佐米、多西他赛、紫杉醇、氟尿嘧啶、依托泊苷均显示了不同程度的负向干扰(P<0.05或P<0.01),其中,吉西他滨、多西他赛、紫杉醇、氟尿嘧啶、依托泊苷的干扰效应均呈剂量依赖性。在ALP酶标反应体系中,与对照组相比,硼替佐米、多西他赛、紫杉醇、依托泊苷、伊立替康、地西他滨、培美曲塞二钠均显示了不同程度的负向干扰(P<0.05或P<0.01),其中,多西他赛、紫杉醇、伊立替康、地西他滨、培美曲塞二钠的干扰效应均呈剂量依赖性。在两种酶反应体系中,多西他赛和紫杉醇在人体血样药物峰浓度时对HRP和ALP酶活性仍具有明显抑制作用。结论:多西他赛、紫杉醇两种化疗药物对HRP和ALP免疫酶促反应体系存在明显干扰作用。

Objective:To explore the interfering effects of common chemotherapy drugs on enzyme-labeled immunoassay.Methods:Interfering drug alkylating agents(cyclophosphamide),antimetabolites(cytarabine,fluorouracil,gemcitabine,decitabine),anti-tumor antibiotics(etoposide),anti-tumor plant component drugs(vincristine,paclitaxel and docetaxel),other anti-tumor drugs(cisplatin,oxaliplatin,carboplatin,nedaplatin and irinotecan)and anti-tumor targeted drugs(bortezomib,hoxetine,pemetrexed disodium)were added into the horseradish peroxidase(HRP)+tetramethylbenzidine(TMB)reaction systems to measure the optical density value with a microplate reader;and the alkaline phosphatase(ALP)+3-(2′-Spiraladamantane)-4-methoxy-4-(3″-phosphoryloxy)benzene-1,2-dioxetane(AMPPD)reaction system to measure the relative luminous intensity with a chemiluminescence instrument.Results:Compared with the control group,in the HRP enzyme-labeled reaction system,all of gemcitabine,bortezomib,docetaxel,paclitaxel,fluorouracil and etoposide produced different degrees of negative interference(P<0.05 or P<0.01).Among them,the interference effects of gemcitabine,docetaxel,paclitaxel,fluorouracil and etoposide were all dose-dependent.In the ALP enzyme-labeled reaction system,compared with the control group,all of bortezomib,docetaxel,paclitaxel,etoposide,irinotecan,decitabine and pemetrexed disodium produced different degrees of negative interference(P<0.05 or P<0.01).Among them,the interference effects of docetaxel,paclitaxel,irinotecan,decitabine,and pemetrexed disodium were all dose-dependent.In the two enzyme reaction systems,docetaxel and paclitaxel still had interference effects at the peak concentration of human blood.Conclusion:Docetaxel and paclitaxel had obvious interference effects on HRP and ALP-labeled immune reaction system.