骨肉瘤多药耐药表型的分化特性及矛盾相关性分析
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作者Author单位AddressE-Mail
曾恒 ZENG Heng 华中科技大学同济医学院附属同济医院矫形外科,湖北 武汉 430030 Department of Orthopaedics,Tongji Hospital Affiliated of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China zengheng@hotmail.com 
陈安民 CHEN An-min 华中科技大学同济医学院附属同济医院矫形外科,湖北 武汉 430030 Department of Orthopaedics,Tongji Hospital Affiliated of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China  
李锋 LI Feng 华中科技大学同济医学院附属同济医院矫形外科,湖北 武汉 430030 Department of Orthopaedics,Tongji Hospital Affiliated of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China  
杨彩虹 YANG Cai-hong 华中科技大学同济医学院附属同济医院矫形外科,湖北 武汉 430030 Department of Orthopaedics,Tongji Hospital Affiliated of Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China  
期刊信息:《中国骨伤》2008年,第21卷,第5期,第368-372页
DOI:doi:10.3969/j.issn.1003-0034.yyyy.nn.zzz
基金项目:科技部973课题子课题 (编号:2002CB513107)
中文摘要:

目的:探讨肿瘤的多药耐药性和恶性程度的关系,主要研究骨肉瘤细胞在向耐药表型的转化过程中,是否出现如骨源性干细胞在成熟分化过程中相似的生物学行为,或者是更复杂的生物学表型。

方法:采用不同表达程度P-gp的骨肉瘤耐药亚型细胞,并针对增殖、分化及转移关键性基因Stathmin及VEGF,应用原位杂交和RT-PCR来衡量Mdr1同Stathmin、VEGF表达的相关性。

结果:Mdr1/P170表型的骨肉瘤细胞的碱性磷酸酶的活性明显高于亲本细胞,说明Mdr表型的骨肉瘤细胞出现了分化。INH和RT-PCR结果揭示Mdr1 mRNA同VEGF、Stathmin mRNA表达呈负相关。

结论:Mdr1/P170的表达预示着骨肉瘤细胞向成熟状态分化,为研究Mdr及其逆转开拓了新的思路,为正确认识P-gp的功能提供了新的研究方法。
【关键词】骨肉瘤  多药耐药相关蛋白质类  血管内皮生长因子
 
Analysis of differentiation characters in osteosarcoma Mdr sublines
ABSTRACT  

Objective: To explore the relationship between multidrug resistance(Mdr)and malignancy. To observe wheth- er P-glycoprotein(P-gp)overexpression had the same bioactivity as osteogenic stem cell turning into more mature cell or more complex phenotype when parent cell line turned to Mdr phenotype.

Methods: Six cell sublines of Mdr phenotype with different expression degree were analyzed. Stathmin generally identified in malignancy cell and stem cell,was a microtubule associated protein and the signal of differentiation in osteogenic stem cell. RT-PCR and hybridization in situ were used to analyze the relationship between Mdr1 mRNA and expression of Stathmin mRNA and VEGF mRNA.

Results: Morphological and functional analysis of Mdr phenotype showed the P-gp-positive cell lines were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase. These subclones all displayed a decrease in potential malignancy such as tumor growth rate and metastatic ability. A significant negative correlation could be identified between Mdr1 mRNA and expression of VEGF and Stathmin mRNA.

Conclusion: Expression of Mdr1/P170 indicated osteosarcoma cells differentiated towards more mature state,which will develop the new research field of Mdr and supply the new research method of the function of P-gp.
KEY WORDS  Osteosarcoma  Multidrug resistance-associataed proteins  Vascular endothelial growth factor(VEGF)
 
引用本文,请按以下格式著录参考文献:
中文格式:曾恒,陈安民,李锋,杨彩虹.骨肉瘤多药耐药表型的分化特性及矛盾相关性分析[J].中国骨伤,2008,21(5):368~372
英文格式:ZENG Heng,CHEN An-min,LI Feng,YANG Cai-hong.Analysis of differentiation characters in osteosarcoma Mdr sublines[J].zhongguo gu shang / China J Orthop Trauma ,2008,21(5):368~372
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