MDR1和GST-π在骨软组织肉瘤中的表达及其与化疗耐药的关系  

Expression of MDR1 and GST-πin osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy resistance

作　　者：魏玲[1] 宋现让[1] 王兴武[1] 李敏[2] 左文述[2] 

机构地区：[1]山东省肿瘤医院基础研究中心,济南250117 [2]山东省肿瘤医院基础研究中心外科,济南250117

出　　处：《中华肿瘤杂志》2006年第6期445-448,共4页Chinese Journal of Oncology

基　　金：山东省卫生厅科研基金资助课题(2001CA1DABA1)

摘　　要：目的探讨多药耐药基因1(MDR1)和谷胱苷肽-S-转移酶-π(GST-π)在骨软组织肉瘤组织中的表达及其与化疗耐药的关系。方法应用荧光定量PCR(FQ-PCR)和流式细胞术(FCM),分别在mRNA水平和蛋白水平检测MDR1和GST-π的表达；以四甲基偶氮唑盐法(MTT)法检测瘤组织对阿霉素(ADM)、顺铂(DDP)、5-氟脲嘧啶(5-Fu)、丝裂霉素C(MMC)、氮烯咪胺(DTIC)、长春新碱(VCR)和氨甲喋呤(MTX)的敏感性。结果患者瘤组织对ADM、DDP、5-Fu、MMC、DTIC、VCR和MTX的不敏感率分别为41．18%、17．65%、47．06%、50．00%、76．47%、61．76%和52．94%。瘤组织中P-gp和GST-π相对荧光强度的表达分别为1．54和为2．58。x^2分析显示,P-gp的表达与ADM耐药、GST-π的表达与ADM、DDP、MMC耐药均呈正相关(P＜0．05)。MDR1和GST-π的表达与患者年龄、性别、病理类型、肿瘤大小均无关(P＞0．05)。GST-π在术前化疗患者的瘤组织中表达升高,且术前表达升高者,术后复发率高于术前GST-π表达水平较低者(P＜0．05)。结论骨软组织肉瘤患者的MDR1、GST-π表达及化疗敏感性存在个体差异；化疗引起GST-π表达上调；原发GST-π高表达是骨软组织肉瘤耐药的主要机制,并与患者预后不良有关。Objective To explore the expression of multidrug resistance gene 1 （MDR1）, glutathione-S-transferases-π （GST-π） in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance. Methods MDR1 and GST-π expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction （FQ-PCR） and flow cytometry （FCM） at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C,daearbazine,vincristine,methotrexate in tumor tissues were detected by MTT assay. Results The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41. 18%, 17.7% ,47. 1% ,50. 0% ,76. 5% ,61. 8% and 52. 9%, respectively. The expression of P-glycoprotein （P-gp） and GST-π in tumor tissues was 1.54 and 2.58 （relative fluorescence intensity ）. X^2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-π expression and resistance on ADM, DDP and MMC （P 〈 0.05）. There was not seen obvious correlation between expression of MDR1, GST-π and age, gender, pathological type, tumor size in osteosareoma and soft tissue sarcoma patients （ P 〉 0.05 ）. The expression of GST-π was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-π expression level than those with lower GST-π expression level before operation （ P 〈 0.05 ）. Conclusion Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-π in osteosareoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-π protein expression. Primary high expression of GST-π is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

关 键 词：多药耐药基因1 谷胱苷肽-S-转移酶-π 骨肉瘤 软组织肉瘤 

分 类 号：R738[医药卫生—肿瘤]