胰岛素样生长因子Ⅰ型受体基因对肝细胞癌生物学行为的影响  

Study of antisense gene to IGF-ⅠR on malignant phenotype of human hepatocellular carcinoma cells

作　　者：周平[1] 周子成[1] 陈文生[1] 刘为纹[1] 房殿春[1] 杨建民[1] 

机构地区：[1]第三军医大学西南医院全军消化专科中心,重庆400038

出　　处：《重庆医学》2003年第9期1166-1169,共4页Chongqing medicine

摘　　要：目的　研究胰岛素样生长因子Ⅰ型受体 (insulin likegrowthfactorⅠreceptor,IGF ⅠR)对肝细胞癌 (hepatocellularcarcinoma ,HCC)生物学行为的影响。方法　应用免疫组化SP法检测肝细胞癌、癌旁和正常肝组织IGF ⅠR的表达。构建IGF ⅠR正、反义基因真核表达载体 ,经脂质体介导转入SMMC 772 1肝癌细胞株 ,观测IGF ⅠR正、反义基因对肝癌细胞生物学行为的影响。结果　 (1)在肝癌组织中IGF ⅠR呈过度表达 (90 .3% ) ,以膜、胞浆混合型表达为主 ,显著高于正常肝组织。肝癌多发结节组高于单发结节组 (P <0 .0 5 )。 (2 )IGF ⅠR反义基因能明显下调内源性IGF ⅠR的表达 ,与 772 1细胞、正义细胞有显著性差异 (P <0 .0 1)。 (3)电镜下反义细胞内可见微腺腔、灶性坏死、髓鞘样结构。 (4 )反义细胞G0 /G1期明显增加 (6 3.9% ) ,S期减少 (19.3% ) ,细胞凋亡增加 (5 .89% ) ,与 772 1细胞、正义细胞有显著性差异 (P <0 .0 1)。 (5 )反义细胞不能在软琼脂中生长。结论　 (1)IGF ⅠR高表达与肝癌的发生及侵袭性行为有密切关系。 (2 )IGF ⅠR反义基因下调 772 1细胞内源性IGF ⅠR的表达 。Objective To study the effect of antisense gene to Ⅰ type of insulin like growth facter (IGF ⅠR) on malignant phontype of SMMC 7721 cell line of human hepatocellular carcinoma. Methods The protein of IGF ⅠR in cancerous and pericancerous tissues of HCC and normal liver tissues were detected by using immunohistochemical SP method. The plasmid vector expressing IGF ⅠR cDNA in the antisense orientation was stably transfected to human HCC cell line SMMC 7721 by using liposome and also observed its effects on malignant phenetype of human HCC cell. Results (1) The expression of IGF ⅠR in cancerous and pericancerous tissues of HCC were higher than that in normal liver tissues, which mainly expressed as a mixture of both membrane and cytoplasm staining (90.3%), with significant difference between in multinodullar and single nodulLar HCC ( P <0.01). (2) The level of endogenous expression of IGF ⅠR was down regulated by IGF ⅠR antisense gene transfection and its level was significant lower than 7721 and sense cells ( P <0.01). (3) Ultrastructure revealed that the antisense cells could be seen many degeneration changes such as myelin finger, focus necrosis and cytoplastic vacuoles. (4) The cell growth curve showed that IGF ⅠR antisense gene could inhibit the cell growth rate after 7 days. The proportion of G1 phase cells (63.9%) and apoptotic cells (5.89%) increased and in contrast, the proportion of S phase cells (19.3%) decreased in the antisense cells, with significant difference between antisense cells and sense and 7721 cells ( P <0.01). (5) The antisense cells could not grow in soft agar, but sense and 7721 cells could grow. Conclusions (1) The expression of IGF ⅠR in cancerous and pericancerous tissues of HCC is higher than that in normal liver tissues which might be related to invasion of HCC and useful for predicting the malignant change of hepatocyte. (2) The level of endogenous expression of IGF ⅠR is significantly down regulated by IGF ⅠR antisense gene which exert

关 键 词：胰岛素样生长因子I型受体 凋亡 肝细胞癌 

分 类 号：R735.7[医药卫生—肿瘤] R730.21[医药卫生—临床医学]