Molecular Pathology of Rat Osteosarcoma and Malignant Fibrous Histiocytoma

1)研究了STI571对大鼠骨肉瘤和MFH细胞系的作用。所有细胞系的细胞生长均受到时间和剂量依赖性的抑制。MFH细胞系的抑制率更高，约为40%，而骨肉瘤细胞系的抑制率约为20%。疗效的差异取决于PDGFRα的表达。2)研究p16^<INK4a>基因在大鼠骨肉瘤、恶性纤维组织细胞瘤及肺腺癌细胞系中的表达及甲基化状态。PCR-SSCP分析显示p16基因在肺腺癌中未表达，而在骨肉瘤和MFHs中的表达与正常成纤维细胞相似。在骨肉瘤中，靠近编码区的区域高度甲基化，而在肺腺癌中，TATA box附近的区域持续甲基化。MFHs和成纤维细胞在这两个区域均低甲基化。3)研究黄吡醇HMR1275对大鼠骨肉瘤、MFH细胞系和肺腺癌细胞系的影响。所有细胞系的细胞生长均受到时间和剂量依赖性的抑制。肺腺癌细胞系的抑制率最高，约为80%，骨肉瘤和MFH细胞系的抑制率约为60%。5-aza - 2'-脱氧胞苷对p16基因的诱导作用增强了HMR1275.4)研究了2-甲氧基雌二醇和组蛋白去乙酰化酶抑制剂对大鼠骨肉瘤和MFH细胞株的作用。2-甲氧基雌二醇和组蛋白去乙酰化酶抑制剂对两种细胞系的细胞生长均有时间和剂量依赖性的抑制作用。目前正在对这些药物的作用机制进行研究，包括缺氧诱导因子、半胱天冬酶等基因的表达。

1)The effect of STI571 was investigated on rat osteosarcoma and MFH cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were greater for MFH cell lines, about 40%, while about 20% for osteosarcoma cell lines. The difference of effectiveness was depend on PDGFRα expression.2)We investigated the expression and methylation status of p16^<INK4a> gene in rat osteosarcoma and malignant fibrous histiocytoma as well as rat lung adenocarcinoma cell lines. The PCR-SSCP analysis showed no expression of p16 gene in lung adenocarcinoma, while similar expression in ostesarcomas and MFHs as normal fibroblasts. The region close to coding region was hypermethylated in osteosarcoma, in contrast, the region nearby TATA box was consistently methylated in lung adenocarcinoma. MFHs and fibroblasts were hypomethylated in both regions.3)The effect of HMR1275 (flavopiridol) was investigated on rat osteosarcoma, MFH cell lines and lung adenocarcinoma cell lines. The cell growth of all cell lines was inhibited in a time- and dose-dependent manner. The inhibition rate were the greatest for lung adenocarcinoma cell lines, about 80%, while about 60% for osteosarcoma and MFH cell lines. The induction of p16 gene by the treatment of 5-aza 2'-deoxycytidine enhances the effects of HMR1275.4)The effects of 2-methoxyestradiol and histone deacethylase inhibitor were investigated on rat osteosarcoma and MFH cell lines. The cell growth of both cell lines was inhibited in a time- and dose-dependent manner by both 2-methoxyestradiol and histone deacethylase inhibitor. The investigation of the effect mechanisms for these drugs is now on-going including the gene expression such as hypoxia inducible factor, caspase etc.