Study of the relationship among expression of Survivin and MRP and the drug resistance in human nasopharyngeal carcinoma
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摘要: 目的:探讨Survivin、多药耐药蛋白(MRP)表达相关性及与鼻咽癌耐药之间的关系。方法:本研究首先采用免疫组织化学法检测Survivin和MRP在45例鼻咽癌和24例正常鼻咽黏膜上皮组织中的表达,分析其表达与鼻咽癌临床病理特征之间的关系;其次,检测Survivin和MRP在31例鼻咽癌紫杉醇耐药患者与20例紫杉醇非耐药患者中的表达,分析它们的表达相关性及其与鼻咽癌耐药的关系;最后采用浓度递增法持续诱导建立鼻咽癌化疗耐药细胞株5-8F-PTX(+),Western blot检测Survivin和MRP在5-8F-PTX(+)和5-8F中的表达情况。结果:Survivin在鼻咽癌组织中的阳性率为71.1%(32/45),明显高于正常鼻咽黏膜组织8.33%(2/24)(P<0.05); Survivin表达与鼻咽癌的分化程度、淋巴结和远处转移以及临床分期有关,与年龄、性别无关;低分化鼻咽癌中Survivin表达阳性率为79.5%(31/39),明显高于中分化鼻咽癌的16.7%(1/6),二者比较差异有统计学意义(P<0.05);Survivin在鼻咽癌化疗耐药患者中表达阳性率为83.9%(26/31),明显高于非耐药患者45.0%(9/20),二者比较差异有统计学意义(P<0.05);MRP在鼻咽癌化疗耐药患者中表达阳性率为87.1%(27/31),明显高于非耐药患者40.0%(8/20),二者比较差异有统计学意义(P<0.05);31例鼻咽癌化疗耐药患者中Survivin和MRP的表达呈正相关;Survivin和MRP在5-8F-PTX(+)中表达水平明显高于非耐药的5-8F;5-8F-PTX(+)耐药细胞株中,紫杉醇、顺铂、5-FU、长春新碱耐药的IC50值均明显高于亲本5-8F组。结论:Survivin表达与鼻咽癌的分化、转移和临床分期有关,可作为鼻咽癌发生、发展的分子标记物;Survivin和MRP高表达与鼻咽癌细胞的耐药性增加有关。Abstract: Objective: This study aimed to explore the relationship among expression of Survivin and MRP and drug resistance in NPC. Method: Expression of Survivin were detected by immunohistochemistry method in 45 cases of NPC and 24 cases of normal mucous membrane of nasopharynx (NMMN).The relationship between expression of Survivin and pathological factors in NPC were analysized. Expression of Survivin and MRP were detected in 31 patients of NPC with paclitaxel resistance and 20 patients of NPC without paclitaxel resistance. The relationship among the expression of Survivin or MRP and paclitaxel resistance in NPC were analysized. The paclitaxel resistance cell line, 5-8F-PTX(+), was established by a step-increased method. The expression of Survivin and MRP were detected by western blot in 5-8F-PTX(+) and 5-8F.Result: The positive were 71.1% (32/45) in NPC and 8.33% (2/24) in NMMN. And there were significantly differences between them(P<0.05). There were relationship among expression of Survivin and differentiation degree, lymph node metastasis, distant metastasis, and clinic stages of NPC. The positive were 75.9% (31/39) in moderately differentiated NPC and 16.7% (1/6) in lowly differentiated NPC, respectively. There were significantly differences between them (P<0.05). The positive of Survivin were 83.9% (26/31) in NPC patients with paclitaxel resistance and 45.0% (9/20) in NPC patients without Paclitaxel resistance, respectively. There were significantly differences between them (P<0.05). The positive of MRP were 87.1% (27/31) in NPC patients with paclitaxel resistance and 40.0% (8/20) in NPC patients without paclitaxel resistance, respectively. There were significantly differences between them (P<0.05). There were positive correlation between the expression of Survivin and MRP in NPC patients with Paclitaxel resistance. The expression of Survivin and MRP were higher in 5-8F-PTX(+) than in 5-8F. The IC50 of paclitaxel, cDDP, 5-FU and Vincristine were significantly higher in 5-8F-PTX(+) than in 5-8F.Conclusion: There were relationship among the expression of Survivin and difference, metastasis and TNM stages of NPC. Survivin may serves as a molecular marker for development and progress in NPC. There were relationship among the high expression of Survivin and MRP and increasing of drug resistance in NPC.
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Key words:
- nasopharyngeal neoplasms /
- drug resistance /
- neoplasm /
- Survivin /
- multidrug-associated protein
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