鼻咽癌多种耐药基因的表达  

Multidrug resistant gene expression in nasopharyngeal carcinoma

作　　者：陶仲强[1] 司勇锋[1] 刘时才[2] 张政[1] 周祥祯[2] 邓卓霞 周日晶[1] 黄波[1] 

机构地区：[1]广西壮族自治区人民医院耳鼻咽喉科,广西南宁530021 [2]广西壮族自治区人民医院病理科,广西南宁530021

出　　处：《中国耳鼻咽喉头颈外科》2007年第2期86-90,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

摘　　要：目的探讨鼻咽癌对化疗药物耐药基因的表达。方法应用单克隆抗体多药耐药基因蛋白(P-glycoprotein,P-gp),多药耐药相关蛋白(multidrug resistance relation protein,MRP),肺耐药相关蛋白(lung-resistance related protein,LRP),拓朴异构酶Ⅱ(topoisomeeraseⅡ,TopoⅡ),胸腺肽合成酶(thymidylate synthase,TS)和谷胱甘肽转移酶(glutathione-S-transferase,GST-π)对56例鼻咽癌患者的肿瘤组织进行免疫组化检测。48例是鼻咽部原发灶组织,其中28例患者用顺氯氨铂(Cisplatin,DDP)+5-氟脲嘧啶(Fluorouracil,5-FU)另20例用卡铂(Carboplatin)+5-FU进行2个疗程化疗,8例是鼻咽癌治疗后颈部淋巴结复发,进行颈淋巴结廓清术。结果各项多药耐药指标在56例患者中均有不同程度表达,它们之间差异有统计学意义,P<0.001,TopoⅡ高表达。鼻咽部原发灶大小T1～T2和T3～T4比较,GST-π的阳性表达差异有统计学意义,P<0.05。初诊患者有无远处转移,P-gp阳性表达比较差异有统计学意义,P<0.01。鼻咽部原发灶和颈部复发淋巴结比较,MRP的阳性表达差异有统计学意义,P<0.05。而患者的性别、年龄和颈部淋巴结大小(N0～N3)比较,各项多药耐药阳性表达差异均无统计学意义,P值均>0.05。P-gp、GST-π和TS阳性组和阴性组用DDP+5-FU化疗,GST-π阳性组和阴性组用卡铂+5-FU化疗,阳性组疗效低于阴性组,P值均<0.05,差异有统计学意义。而TopoⅡ高表达,其阳性组化疗疗效均优于阴性组。对DDP+5-FU和卡铂+5-FU的疗效进行比较,P值均<0.05,差异有统计学意义。结论鼻咽癌组织存在多种多药耐药基因表达,是鼻咽癌的化疗主要的障碍。进一步研究鼻咽癌多药耐药基因的表达和对化疗的反应是必要的。OBJECTIVE To study the expression of multidrug resistant （MDR） gene in nasopharyngeal carcinoma（NPC）. METHODS The specimens from 56 case of NPC were studied by immunohistochemistry for monoclonal antibodies of P-glycoprotein（P-gp）, multidrug resistance relation protein （MRP）, lungresistance related protein（LRP）, topoisomeerase Ⅱ （TopoⅡ）, thymidylate synthase（TS）, glutathione-Stransferase（GST-π ）. Among them, 48 specimens were taken from primary lesion, in which 28 cases had received two courses chemotherapy with DDP＋5- FU（PF） and other 20 cases with Carboplatin＋5-FU（CF）. Other 8 specimens were taken from the cervical lymph-node recurrence lesion after neck dissection. RESULTS All the 56 specimens demonstrated different expression of MDR genes in different degree. The difference of expression among different MDR genes was statistically significant（P〈 0.001 ）.The expression of Topoilwas more frequent in NPC. There was a significant difference between GST-π expression in T1-T2 and T3-T4 lesions, P-gp expression in M0 and M1 lesions, MRP expression in primary and lymphnode lesions. There were no significant difference among expressions of different MDR genes with sex, age and lymph-node（N0-N3）.The effective rates of chemotherapy with DDP＋5-FU in patients with expression of P-gp, GST-Tr and TS was lower than that with no expression （P〈0.05）. GST-π expression correlated with a lower response to chemotherapy with Carboplatin＋5-FU than with no-expression （P〈0.05）.But Topo Ⅱ over expression correlated with a higher response to chemotherapy with DDP＋5-FU and Carboplatin＋5-FU than with no-expression （P〈0.05）. CONCLUSION These results suggest that the drug resistance gene expression is of crucial impact on chemotherapy for NPC patients. Study of the expression of MDR and its relationship with the chemotherapeutic sensitively in NPC patients is needed.

关 键 词：鼻咽肿瘤 多药耐药相关蛋白类 抗肿瘤联合化疗方案 

分 类 号：R739.63[医药卫生—肿瘤]