[骨肉瘤和软组织肉瘤中MDR1和GST-pi的表达及其与化疗耐药的相关性]

[Expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy resistance].

作者信息

Wei Ling, Song Xian-Rang, Wang Xing-Wu, Li Min, Z uo Wen-Shu

机构信息

Cancer Research Center of Shandong Tumor Hospital, Jinan 250117, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2006 Jun;28(6):445-8.

PMID:17152492

Abstract

OBJECTIVE

To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.

METHODS

MDR1 and GST-pi 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, dacarbazine, 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-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).

CONCLUSION

Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

摘要

目的

探讨多药耐药基因1（MDR1）、谷胱甘肽S转移酶π（GST - π）在34例骨肉瘤及软组织肉瘤组织中的表达情况及其与化疗耐药的相关性。

方法

分别采用实时荧光定量聚合酶链反应（FQ - PCR）和流式细胞术（FCM）从mRNA和蛋白水平分析MDR1和GST - π的表达。采用MTT法检测肿瘤组织对阿霉素、顺铂、氟尿嘧啶、丝裂霉素C、达卡巴嗪、长春新碱、甲氨蝶呤的化疗敏感性。

结果

肿瘤组织对阿霉素、顺铂、氟尿嘧啶、丝裂霉素C、达卡巴嗪、长春新碱、甲氨蝶呤的不敏感率分别为41.18%、17.7%、47.1%、50.0%、76.5%、61.8%和52.9%。肿瘤组织中P - 糖蛋白（P - gp）和GST - π的表达分别为1.54和2.58（相对荧光强度）。χ²分析显示，P - gp表达与阿霉素耐药呈正相关，GST - π表达与阿霉素、顺铂和丝裂霉素C耐药呈正相关（P < 0.05）。骨肉瘤和软组织肉瘤患者中MDR1、GST - π表达与年龄、性别、病理类型、肿瘤大小未见明显相关性（P > 0.05）。接受术前化疗患者的GST - π表达升高。术前GST - π表达水平高的患者术后复发率高于表达水平低的患者（P < 0.05）。