环氧化酶-2抑制剂与抗癌药对鼻咽癌细胞抑制的相互作用

Interaction of Inhibiting Effect of Cyclooxygenases-2 and Anticancer Drugs on Nasopharyngeal Carcinoma Strains

目的:探讨环氧化化酶-2（COX-2）抑制剂与细胞毒抗癌药对鼻咽癌细胞抑制的相互作用。方法:COX-2抑制剂（尼美舒利和塞莱昔布）单用或分别与顺铂（CDDP）,博来霉素（BLM）,长春新硷（VCR）联合给药,用噻唑蓝法观察用药对鼻咽癌细胞系CNEI,CNE2和SUNE的细胞毒作用,经S-N-K法统计学检验后再用金正钧氏法q值判断COX-2抑制剂与细胞毒抗癌药的相互作用。结果:尼美舒利25μmol·L-1分别与BLM 0.5,1,2mg·L-1,CDDP6.25,12.5mg·L-1和VCR1mg·L-1合用,CNEI细胞系的抑制率分别为33％,47％,48％,59％,63％,32％（与单用比较,P<0.05或P<0.01,q值分别为1.88,2.54,1.65,2.70,1.37,1.45）,呈协同作用。尼美舒利25μmol·L-1分别与CDDP1,2.5mol·L-1合用,CNE2细胞系的抑制率分别为33％和25％（与单用比较,P<0.05或P<0.01q值分别为0.69和0.32）,呈拮抗作用。尼美舒利25μmol·L-1分别与CDDP6.25,125mg·L-1合用,对SUNE细胞系的抑制率分别为21％和17％（与单用比较,P<0.05或P<0.01,q值分别为0.50和0.21）,呈拮抗作用。塞莱昔布2.5μmol·L-1分别与BLM,2mg·L-1,CDDP12.5mg·L-1和VCR1mg·L-1合用,CNE1细胞系的抑制率分别为43％,58％,50％,39％（与单用比较,P<0.05或P<0.01,q值分别为1.59,1.61,1.43,1.49）,呈协同作用。塞?

OBJECTIVE: To study interaction of inhibiting effects of cyclooxygenase-2 (COX-2) inhibitors and anticancer drugs on nasopharyngeal carcinoma (NPC) cells. METHODS: Inhibiting action of COX-2 inhibitors and cytotoxic drugs on NPC strains (CNE1, CNE2, SUNE) was observed by MTT assay. Interaction of COX-2 inhibitors and anticancer drugs was estimated by S-N-K statistic analysis and q value provided by Jin Zheng-jun's method. RESULTS: Synergistic effects showed in inhibiting action of CNE1 strain after dosingNim (nimesulide) 25 μ mol·L-1/BLM (bleomycin) 0.5,1,2 mg·L-1,Nim μ mol·L-1/CDDP (cisplatin) 6.25,12.5mg·L-1 and Nim 25 1M/VCR (vincrestine)l mg·L-1. Inhibiting rates for CNE1 strain were 33%,47%,48%,59%,63% and 32%, respectively (compared with single drugs, P<0.05 or P<0.01,q value : 1.88,2.54,1.65,2.70,1.37 and 1.45 respectively). Antagonism manifested in inhibiting action of CNE2 strain after dosing Nim 25 μ mol·L-1/ CDDP 1,2.5 mg·L-1, Inhibiting rates for CNE2 strain were 33% or 25%, respectively (compared with single drug, P<0.05 or P<0.01,q: 0.69 and 0.32). Antagonism in inhibiting action of SUNE strain exhibited in Nim 25 μ mol·L-1/CDDP 6.25,12.5mg·L-1, inhibiting rates for SUNE strain were 21% or 17% , respectively (compared with single drug, P<0.05 or P<0.01,q: 0.50 and 0.21). Synergistic effect represented in inhibiting action of CNE1 strain after dosing Cel (celecoxib) 2.5 μ mol·L-1/BLM 1,2mg·L-1,Cel 2.5 μ mol·L-1/CDDP 12.5 mg·L-1, Cel 2.5 μ mol·L-1/ VCR 1 mg·L-1 .Inhibiting rates for CNE1 strain were 43%,58%,50%,39% , respectively (compared with single drug, P<0.05 or P<0.01,q: 1.59,1.61,1.43,1.49). Additivity effect appeared in inhibiting action of SUNE strain after dosing Cel 2.5 μ mol· L-1/ BLM 0.5 mg·L-1 or CDDP 6.25mg·L-1 .Inhibiting rates for CNE1 strain were 29%,23%, respectively (compared with single drug, P<0.05 or P<0.01,q:1.11,1.02). Synergistic effect represented in inhibiting action of SUNE strain after dosing Cel 2.5 μ mol·L-1/BLM 1,2mg·L-1, or CDDP 6.25,or 12.5mg·L-1, Inhibiting rates for SUNE strain were 16%,60%,19%,48%, respectively (compared with single drug, P<0.05 or P<0.01,q: 1.45,1.91,1.23,1.57). CONCLUSION: Synergism or additivity of inhibition to CNE1 strain caused by combination dosing of nimesulide with BLM or CDDP or VCR, whereas antagonism of inhibition to CNE2 and SUNE strains was seen in combination dosing of nimesulide with CDDP. Synergism or additivity of inhibition to CNE1 and SUNE strains showed in concomitances of celecoxib with BLM, or CDDP, or VCR.