骨软组织肉瘤中耐药相关蛋白表达及与化疗耐药的相关性  

Expression of drug resistance related proteins in osteosarcoma and soft tissue sarcoma and its correlations with chemotherapy resistance

作　　者：宋现让[1] 魏玲[1] 王兴武[1] 李敏[1] 

机构地区：[1]山东省肿瘤医院基础研究中心,山东济南250117

出　　处：《中国病理生理杂志》2006年第10期2012-2017,共6页Chinese Journal of Pathophysiology

基　　金：山东省卫生厅科研基金资助课题(No.2001CA1DABA1)

摘　　要：目的:探讨4种耐药相关蛋白-P-糖蛋白(P-gp)、谷胱甘肽S-转移酶-π(GST-π)、肺耐药蛋白(LRP)和多药耐药相关蛋白(MRP)在骨肉瘤细胞株Saos2和U2OS以及34例骨软组织肉瘤的表达及与化疗耐药的关系。方法:应用流式细胞术(FCM)检测蛋白表达;MTT法评估化疗耐药。结果:Saos2细胞耐药相关蛋白的表达低于U2OS,阿霉素(ADM)、顺铂(DDP)、5-氟脲嘧啶(5-Fu)、丝裂霉素(MMC)、氮烯咪胺(DTIC)和长春新碱(VCR)的敏感性高于U2OS。两细胞株经1/5半数抑制浓度(IC50)的ADM和DDP分别处理24 h后,GST-π增幅达33%-43%。34例患者对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%。肿瘤组织P-gp、GST-π、LRP和MRP表达分别为1.54、2.58、1.91和1.86。相关分析显示,P-gp表达与ADM耐药呈正相关(r=0.485,P<0.01),GST-π表达与ADM、DDP、5-Fu、MMC耐药呈正相关(r分别为0.402、0.458、0.364和0.500,P值分别为<0.05、<0.01、<0.05和<0.01)。耐药相关蛋白在不同性别、不同年龄、不同病理类型、不同肿瘤大小患者间的表达差异均无显著(P>0.05)。经术前化疗的患者GST-π表达显著升高,且随访复发患者术前GST-π表达显著高于无复发患者(P<0.05)。结论:骨软组织肉瘤患者耐药相关蛋白表达及化疗敏感性存在显著个体差异。化疗可引起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预后有关。AIM： To explore the expression of four kinds of drug resistance related protein： P - glycoprotein （ P - gp）, glutathione - S - transferases -π （ GST -π）, lung resistance protein （LRP） , muhidrug resistance related protein （MRP） in osteosarcoma cell lines Saos2 and U2OS, and in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlations with chemotherapy resistance. METHODS： The expression of protein was detected by flow cytometry （FCM）. Chemotherapy resistance was analyzed by MTT assay. RESULTS： Expression of drug resistance related protein was lower in Saos2 cell line than that in U2OS cells. Chemotherapy sensitivity on adriamycin （ADM）, cisplatinum （DDP）, fluorouracilum （5- Fu）, mitomycin （MMC）, dacarbazine （DTIC） , vincristine （VCR） was higher in Saos2 than those in U2OS cells. After the two cell lines were treated respectively with 1/5 50% inhibitory concentration （ IC50 ） doses of ADM and DDP, the expression increasing range of GST-π was 33% -43%. The nonsensitive rate on ADM, DDP, 5 -Fu, MMC, DTIC, VCR, methotrexate （MTX） in 34 patients were 41. 18%, 17.65%, 47.06%, 50. 00%, 76. 47%, 61.76% and 52.94% , respectively. The expression of P - gp, GST -π, LRP, MRP were 1.54, 2.58, 1.91 and 1, 86, respectively. The correlation analysis showed that the expression of P - gp had positive correlation with resistance on ADM （ r = 0. 485, P 〈0. 01 ）, the expression of GST -π had correlations with resistance on ADM, DDP, 5 - Fu and MMC. The r value was 0. 402, 0. 458, 0, 364 and 0. 500, respectively. The corresponding value of P was 〈0. 05, 〈 0. 01, 〈0. 05 and 〈 0. 01, respectively. The observed expression of resistance related proteins was not significant difference between different gender, different age, different pathological type and different tumor size in osteosarcoma and soft tissue sarcoma patients （P 〉 0. 05）. The expression of GST -π was increased dramatically in patients receiving chemotherapy preop

关 键 词：骨肉瘤 软组织肿瘤 P糖蛋白类 多药耐药相关蛋白质类 流式细胞术 

分 类 号：R738[医药卫生—肿瘤] R730.49[医药卫生—临床医学]