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作 者:吴乔 陈玉强[1] 陈正明[2] 陈福 苏文金[2]
机构地区:[1]Hospital 174,PLA,Xiamen361003,China [2]厦门大学生命科学学院细胞生物学与肿瘤细胞工程教育部重点实验室
出 处:《Acta Pharmacologica Sinica》2002年第9期835-841,共7页中国药理学报(英文版)
基 金:Supported by the National Outstanding Youth Science Foundation of China(B type,№ 39825502);the National Natural Science Foundation of China(№ 39880015);Key Project of Science&Technology of the Ministry Education(00073).
摘 要:AIM: To investigate the effects of all-trans retinoic acid (ATRA) on metastasis and its related proteins in human gastric cancer cells in vivo and in vitro. METHODS: Gastric cancer cells, MGC80-3 and SGC-7901, were inoculated into spleen subcapsule of nude mice, respectively. Nude mice were administered with ATRA (0.7 mg/ kg, ig) every other day. Six weeks later, nude mice were sacrificed. All the tumors formed in spleen and in liver were removed. Some of them were fixed, and then embedded. Others were kept in liquid nitrogen for further use. Expression level of proteins in tumor and in cell was analyzed by Western blot. Microvessel in tumor section was shown by immunohistochemistry and adhesive ability of cell to amnion was measured by adhesion assay. RESULTS: When inoculated nude mice were treated with ATRA, the xenograft tumors in spleen and metastatic tumors in liver were suppressed by 50 % respectively, and inhibition of microvessel formation in xenograft and metastatic tumors was also observed obviously. Although ATRA regulated expression of nm23 and mtsl/pl6 proteins at different patterns in vivo and in vitro, high ratio of nm23:mtsl/p16 was in association with low adhesive activity of cells. In addition, ATRA induced ICAM-1 protein expression in vivo and in vitro. CONCLUSION: ATRA inhibits the growth of xenograft tumors and their metastasis to liver. This process may be associated with regulation of metastatic related proteins, including nm23, mtsl/p16, and ICAM-1 in vivo and in vitro.目的:从体内外探讨全反式视黄酸(ATRA)对人胃癌细胞转移及其相关蛋白影响.方法:胃癌细胞接种到裸鼠脾包膜,每隔两天灌胃给予ATRA 0.7 mg/kg,6周后处死裸鼠,取出所有在脾和肝形成的肿瘤,一些肿瘤被固定和包埋,另一些肿瘤保存在液氮中用于后续实验.用蛋白质印迹法测定蛋白水平;通过免疫组化显示微血管;采用粘附实验测定细胞粘附能力.结果:ATRA灌胃后,脾移植瘤和肝转移瘤受到明显抑制(50%),血管生成也受到抑制.尽管ATRA在体内外调节nm23和mts1/p16蛋白的方式不同,但高比值的nm23:mtsl/p16与低粘附性相关.ATRA在体内外诱导ICAM-1蛋白表达.结论:ATRA显著抑制移植瘤生长及其向肝转移,这一过程可能与对转移相关蛋白nm23,mstl/p16和ICAM-1的调控有关.
关 键 词:TRETINOIN neoplasm metastasis stomach neoplasms nude mice
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