中文摘要
骨肉瘤是一种好发于青少年的原发性高度恶性肿瘤,具有恶性程度高、肺转移早、致残率高、复发率高等临床特点。随着分子生物学的发展,基因治疗在骨肉瘤治疗中的作用逐渐被重视。核仁素是真核细胞核仁中的一种磷酸蛋白质,具有多种生物学功能。本研究通过分析核仁素在骨肉瘤组织、细胞系中的表达模式,采用反义寡核苷酸技术和转基因技术研究核仁素在骨肉瘤细胞中表达下调与上调对顺铂(DDP)诱导人骨肉瘤细胞增殖、凋亡的影响及其分子生物学机制。结果发现:(1)核仁素在大多数骨肉瘤组织中高表达;核仁素在骨肉瘤组织中阳性表达率与肿瘤的恶性程度呈正相关。(2)核仁素表达下调能促进DDP诱导的SaOS-2细胞增殖抑制和凋亡。(3)核仁素过表达能抑制DDP诱导的SaOS-2细胞增殖抑制和凋亡。(4) 核仁素在骨肉瘤细胞中的表达水平与骨肉瘤细胞bcl-2 mRNA稳定性呈正相关。
英文摘要
Osteosarcoma is the most common high grade primary bone tumor with a high degree of early lung metastasis and a high rate of deformity. It occurs in adolescents and children. With the development of molecular Biology, gene therapy was used more often to heal it. Nucleolin is a phosphoric acid protein in eukaryotic nucleolar, with a variety of biological functions. This study was to analyze the expression patterns of nucleolin in osteosarcoma cell line and tissue, and use antisense technology and transgenic technology to probe into the relationship of C23 with osteosarcoma and to observe the effect of C23 on inhibition of proliferation and apoptosis induced by cisplatin in human osteosarcoma cells and its molecular mechanism. The results showed that:(1). A high expression of C23 was found in osteosarcoma tissue. And the expression of nucleolin had positive correlation with malignant degree. (2). Down-regulation of C23 could contribute to cisplatin-mediated inhibition of proliferation and apoptosis in osteosarcoma cells. (3). Over-expression of C23 could increase resistance of SaOS-2 cells to cisplatin. (4). The Expression levels of nucleolin in osteosarcoma cells was positively correlated with bcl-2 mRNA stability.
结题摘要
骨肉瘤是一种好发于青少年的原发性高度恶性肿瘤,具有恶性程度高、肺转移早、致残率高、复发率高等临床特点。随着分子生物学的发展,基因治疗在骨肉瘤治疗中的作用逐渐被重视。核仁素是真核细胞核仁中的一种磷酸蛋白质,具有多种生物学功能。本研究通过分析核仁素在骨肉瘤组织、细胞系中的表达模式,采用反义寡核苷酸技术和转基因技术研究核仁素在骨肉瘤细胞中表达下调与上调对顺铂(DDP)诱导人骨肉瘤细胞增殖、凋亡的影响及其分子生物学机制。结果发现:(1)核仁素在大多数骨肉瘤组织中高表达;核仁素在骨肉瘤组织中阳性表达率与肿瘤的恶性程度呈正相关。(2)核仁素表达下调能促进DDP诱导的SaOS-2细胞增殖抑制和凋亡。(3)核仁素过表达能抑制DDP诱导的SaOS-2细胞增殖抑制和凋亡。(4) 核仁素在骨肉瘤细胞中的表达水平与骨肉瘤细胞bcl-2 mRNA稳定性呈正相关。
