缺氧诱导因子1α表达对裸鼠肝癌皮下移植瘤生长的促进作用  

Effects of hypoxia-inducible factor 1α on the growth of subcutaneously implanted hepatocellular carcinoma in nude mice

作　　者：金炜东[2] 陈孝平[1] 杨盛利[1] 张万广[1] 靖凯[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科,武汉430030 [2]广州军区武汉总医院普通外科

出　　处：《中华普通外科杂志》2008年第10期788-790,共3页Chinese Journal of General Surgery

基　　金：国家自然科学基金资助（30371395）

摘　　要：目的探讨缺氧诱导因子1α表达对肝癌移植瘤生长的影响。方法建立强力霉素诱导缺氧诱导因子1α表达的裸鼠肝癌HepG2^Tet-on-HIF-1α细胞皮下移植瘤模型；荷瘤裸鼠口服强力霉素（Dox）后，观察上调缺氧诱导因子1α对皮下移植瘤生长的影响。结果荷瘤裸鼠口服强力霉素可以上调裸鼠皮下移植瘤中缺氧诱导因子1α mRNA和蛋白表达水平；肿瘤体积Dox（＋）组vs．Dox（-）组为（513．545±276．229）mm^3 vs．（166．506±110．142）mm^3（P〈0．05），肿瘤重量（1．251±0．438）g vs．（0．640±0．296）g（P〈0．05），肿瘤生长速度Dox（＋）组明显超过Dox（-）组，肿瘤内面积坏死率明显小于Dox（-）组（31．360％±2．728％）vs．（36．640±3．804％）（P〈0．05）；同Dox（-）组相比，Dox（＋）组裸鼠体重下降更为明显（P〈0．01）。两组荷瘤鼠均无肝、肺转移发生。结论强力霉素可以诱导裸鼠肝癌HepG2^Tet-on-HIF-1α细胞皮下移植瘤模型中缺氧诱导因子1α的表达，促进肿瘤的生长。Objective To study the effects of HIF-1α expression on the growth of subcutaneously implanted human hepatocellular carcinoma （ HCC ） cell lines in nude mice. Methods A nude mouse model of subcutaneously implanted HCC cell line HepG2^Tet-on-HIF-1α was established. This cell lines characterizes the inducible expression of HIF-1α by doxycyeline （Dox）. The impact of HIF-1α expression induced by Dox on the growth of subcutaneously implanted HCC cell lines in the nude mouse model was observed. Results The mRNA and protein expression of HIF-1α were significantly up-regulated in the nude mouse model by oral administration of Dox. Compared with that model in which Dox was not administrated ie Dox（ - ）group, the tumor volume（513. 545 ±276. 229） mm^3 vs. （166. 506 ± 110. 142） mm^3 （ P 〈 0. 05 ） , tumor weight （ 1.251 ± 0. 438 ） g vs. （ 0. 640 ± 0. 296 ） g （ P 〈 0. 05 ）, and tumor growth velocity were significantly enhanced in Dox （ ＋ ） group, while tumor necrosis was inhibited （31. 360% ± 2. 728% vs. 36. 640% ±3. 804% ） （P 〈0. 05）. The weight loss of nude mice was larger in Dox（ ＋ ）group （ P 〈 0. 01 ）. There was no liver or lung metastasis in either group. Conclusion The expression of HIF-1α in subcutaneously implanted HCC in a nude mouse model is up-regulated by oral Dox. High grade expression of HIF-1α promotes the growth of implanted HCC.

关 键 词：肝肿瘤 基因表达 缺氧诱导因子1 Α亚基 动物实验 

分 类 号：R686[医药卫生—骨科学]