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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 investigate the expression of multidrug resistance-1 (MDR1) and glutathione-S-transferase-π (GST-π) in osteosarcoma sarcoma and its relationship with chemoresistance. Methods The expression of MDR1 and GST-π was detected by FQ-PCR and FCM respectively at the level of mRNA and protein. The expression of MDR1 and GST-π was detected by MTT assay (ADM), cisplatin (DDP), 5-fluorouracil (5-Fu), mitomycin C (MMC), dicalcium (VCR), vincristine Methotrexate (MTX) sensitivity. Results The insensitivity rates of tumor tissues to ADM, DDP, 5-Fu, MMC, DTIC, VCR and MTX were 41.18%, 17.65%, 47.06%, 50.00% and 76.47% , 61.76% and 52.94% respectively. The relative fluorescence intensity of P-gp and GST-π in tumor tissues were 1.54 and 2.58, respectively. The results of x ~ 2 showed that the expression of P-gp was resistant to ADM and the expression of GST-π was positively correlated with the drug resistance of ADM, DDP and MMC (P <0.05). The expression of MDR1 and GST-π had no correlation with age, sex, pathological type and tumor size (P> 0.05). The expression of GST-π was increased in the tumor tissues of patients with preoperative chemotherapy, and the expression of GST-π was significantly higher than that of preoperative GST-π expression (P <0.05). Conclusion The expression of MDR1, GST-π and chemosensitivity in osteosarcoma sarcoma have individual differences. Chemotherapy induced the up-regulation of GST-π. Primary GST-π overexpression is the main mechanism of osteosarcoma resistance in osteosarcoma, and is associated with poor prognosis related.