骨肉瘤诱导分化与多药耐药表型的生物学性状比较

Biobehaviorer differencement between differentiated phenotype and MDR phenotype of osteosarcoma

[目的]探讨诱导分化剂诱导骨肉瘤分化时同骨肉瘤耐药状态产生的分化情况的异同点,以便正确认识分化与耐药相关性。[方法]以诱导分化剂ATRA,IL-4处理人成骨肉瘤细胞系,对比MG-63耐药表型MG-63/R,观察瘤细胞生物学性状。用原位杂交分析在这一转化过程上凋亡调控基因P53,bcl-2 mRNA表达,用Tunel法分析细胞的凋亡。MTT法检查细胞对药物敏感性。[结果]MG-63/R,以及IL-4,ATRA处理的MG-63,细胞均出现分化,AT-RA处理的MG-63表现多药耐药性,并同MG-63/R表现出了相似的特性而IL-4处理的细胞分化的同时并未出现耐药。[结论]肿瘤细胞分化的过程中有可能出现一种顽固的多药耐药的亚分化状态,这种差异性分化的产生可能同细胞种类、状态、药物作用特点及剂量有关,如何控制细胞向耐药状态的分化为肿瘤的治疗提出了新的难题。

[ Objective] To investigate the relationship beween muhidrug -resistance （MDR） behavior in duced by differentiation induced agents and differentiation behavior of MDR phenotype of osteosarcoma. [ Method ] ATRA and IL-4 was used to treat human osteoblast. Osteosarcoma cell line MG-63. The proliferative activity, activity of cellular alkalin phosphatase, and cell cycle distribution of tumor cells was used to evaluated the degree of cell differentiation and match the differentiation behavior of MDR phenotype cell subline. Westenblot was use to detected P-gp expression change of the several differentiated cell sublines. In situ hybrization was use to detected the expression levels of p53. bel-2 mRNA, and Tunel＇s method was used to detected the apoptosis of the cell sublines respectively. [ Result ] Three sublines have differentiated. The cell subline treated by ATRA led to drug resistence and apoptosis rate have not significant difference compared with parent cells （ P 〉 0.05 ）ans MDR phenotype cell sublines. But the cell subline treated by IL-4 have significant changes in every levels （ P 〉 0. 05 ）. [ Conclusion] During differentiation, osteosarcorma cell may turn into multidrug-resistance phenotype, a obstinate subdifferentiated phenotype.