Osteosarcoma is the most common primary malignant neoplasm of the bone in children and adolescents and has a high risk of relapse and metastasis. Of the various methods to treat osteosarcoma, the use of genetic approa...Osteosarcoma is the most common primary malignant neoplasm of the bone in children and adolescents and has a high risk of relapse and metastasis. Of the various methods to treat osteosarcoma, the use of genetic approaches to inhibit the rapid growth of osteosarcoma while limiting tumor metastasis has presented a challenge in its implementation. Here, we successfully synthesized a polysaccharide derivative （Amy-g-PLLD） for delivery of astrocyte elevated gene-1 （AEG-1） small-interfering RNA （siRNA） （siAEG-1）, and used it for the first time to suppress osteosarcoma tumors in vitro and in vivo. Amy-g-PLLD/ siAEG-1 complexes were delivered into 143B human osteosarcoma cells with low resultant cytotoxicity. Osteosarcoma tumor proliferation and invasion were inhibited in vitro. Intratumoral injection of Amy-g-PLLD/siAEG-1 complexes markedly inhibited tumor growth and lung metastasis in 143B tumor-bearing mice. This biocompatible and effective approach employing a natural material- siRNA complex should pave the way for more genetic research in treating osteosarcoma.展开更多
目的研究上调AEG-1在体内外对人骨肉瘤细胞增殖和生长能力的影响。方法通过慢病毒转染法建立AEG-1高表达MG63稳定转染细胞株,用q RT-PCR和Western-blot检测AEG-1 m RNA和蛋白水平的变化,分别用MTT法和流式细胞术检测AEG-1对MG63细胞增...目的研究上调AEG-1在体内外对人骨肉瘤细胞增殖和生长能力的影响。方法通过慢病毒转染法建立AEG-1高表达MG63稳定转染细胞株,用q RT-PCR和Western-blot检测AEG-1 m RNA和蛋白水平的变化,分别用MTT法和流式细胞术检测AEG-1对MG63细胞增殖能力和细胞周期的影响,通过鸡胚尿囊膜移植瘤实验检测AEG-1对人骨肉瘤生长能力的影响。结果与对照组比较,AEG-1 m RNA和蛋白水平显著升高,上调AEG-1明显增强MG63细胞的增殖能力,使G1期细胞比率明显减少,S期和G2期细胞比率明显增加,稳定转染AEG-1组MG63细胞鸡胚尿囊膜移植瘤体积明显增大。结论上调AEG-1可提高MG63细胞的增殖能力,促进MG63细胞鸡胚尿囊膜移植瘤的生长。展开更多
基金This work was supported by the National Natural Science Foundation of China （Nos. 81402221 and 51273216）, the Research Fund for the Doctoral Program of Higher Education of China （No. 20130171120077）, the Science and Technology Program of Guangzhou, China （No. 201707010108）, the Guangdong Innovative Research Team Program （No. 2009010057）, and the Science and Technology Planning Project of Guangzhou （No. 201610010006）, the Science and Technology Planning project of Guangdong Province （No. 20153900042020319） and Natural Science Foundation of Guangdong Province （No. 2016A030313819）.
文摘Osteosarcoma is the most common primary malignant neoplasm of the bone in children and adolescents and has a high risk of relapse and metastasis. Of the various methods to treat osteosarcoma, the use of genetic approaches to inhibit the rapid growth of osteosarcoma while limiting tumor metastasis has presented a challenge in its implementation. Here, we successfully synthesized a polysaccharide derivative （Amy-g-PLLD） for delivery of astrocyte elevated gene-1 （AEG-1） small-interfering RNA （siRNA） （siAEG-1）, and used it for the first time to suppress osteosarcoma tumors in vitro and in vivo. Amy-g-PLLD/ siAEG-1 complexes were delivered into 143B human osteosarcoma cells with low resultant cytotoxicity. Osteosarcoma tumor proliferation and invasion were inhibited in vitro. Intratumoral injection of Amy-g-PLLD/siAEG-1 complexes markedly inhibited tumor growth and lung metastasis in 143B tumor-bearing mice. This biocompatible and effective approach employing a natural material- siRNA complex should pave the way for more genetic research in treating osteosarcoma.
文摘目的研究上调AEG-1在体内外对人骨肉瘤细胞增殖和生长能力的影响。方法通过慢病毒转染法建立AEG-1高表达MG63稳定转染细胞株,用q RT-PCR和Western-blot检测AEG-1 m RNA和蛋白水平的变化,分别用MTT法和流式细胞术检测AEG-1对MG63细胞增殖能力和细胞周期的影响,通过鸡胚尿囊膜移植瘤实验检测AEG-1对人骨肉瘤生长能力的影响。结果与对照组比较,AEG-1 m RNA和蛋白水平显著升高,上调AEG-1明显增强MG63细胞的增殖能力,使G1期细胞比率明显减少,S期和G2期细胞比率明显增加,稳定转染AEG-1组MG63细胞鸡胚尿囊膜移植瘤体积明显增大。结论上调AEG-1可提高MG63细胞的增殖能力,促进MG63细胞鸡胚尿囊膜移植瘤的生长。
