中国肿瘤生物治疗杂志2011，Vol.18Issue(4)：368-372,5.DOI:10.3872/j.issn.1007-385X.2011.04.005
KLF4对肿瘤干细胞自我更新和增殖潜能的影响
Effect of KLF4 on self-renewal and proliferation potential of tumor stem cells
摘要
Abstract
Objective; To explore the effect of Kriippel-like factors 4 ( KLF4) on self-renewal and proliferation potential of tumor stem cells (T3A-A3). Methods; A lentiviral vector carrying shRNA targeting KLF4 (pLVTHM-shKLF4) was constructed. Tumor stem cells (T3A-A3 cells) were isolated from a human hepatocarcinoma and were identified in our previous study. The expression of KLF4 mRNA and protein in T3A-A3 cells was analyzed by RT-PCR and Western blotting analysis after pLVTHM-shKLF4 infection. Self-renewal ability of T3A-A3 cells was evaluated by tumor sphere formation assay after pLVTHM-shKLF4 infection; clonogenic assay was used to determine the clonogenic ability of T3A-A3 cells; and cell cycle phase distribution was analyzed by flow cytometry. Influence of KLF4 knockdown on the growth of T3A-A3-transplanted tumors was examined in xenograft model of nude mice. Results; T3A-A3 expressed higher level of KLF4 than human hepatocarcinoma cell line Bel-7402 and HepG2. pLVTHM-shKLF4 infection significantly decreased the expression of KLF4 mRNA and protein in T3A-A3 cells. The formed tumor spheres of T3A-A3 cells were significantly smaller in pLVTHM-shKLF4 infection group compared with that in the pLVTHM-shNC control group ([ 104. 33 ± 16.28] ixm vs [186.67 ±28. 151 am, P＜0.01). pLVTHM-shKLF4 infection significantly inhibited the number of T3A-A3 cellcolonies compared with control group (83. 5 ± 7. 78 vs 125 ±9. 19, P ＜ 0. 01 ). Flow cytometry analysis showed that pLVTHM-shKLF4 infection significantly increased G, population when compared with the control vector ( [ 39. 65 ± 4. 03 ] % vs [29.35 ± 1. 00 ] % , P ＜ 0. 01). Furthermore, the growth of T3A-A3-transplanted tumors in pLVTHM-shKLF4 infection group was significantly slower than that in the control group (33 days after cell inoculation, [46. 14 ± 12. 94 ] vs [ 228.12 ± 94. 86 ] mm3, P ＜ 0.01). Conclusion: KLF4 knockdown can inhibit the self-renewal of tumor stem cells (T3A-A3 cells) , and inhibit the proliferation potential of T3A-A3 both in vitro and in vivo.关键词
Krüppel样因子4(KLF4)/RNA干扰/肝癌/肿瘤干细胞/T3A-A3/自我更新/增殖Key words
Krtippel-like factor4 (KLF4)/ RNA interference/ hepatocellular carcinoma/ tumor stem cell/ T3A-A3/self renewal/ proliferation分类
医药卫生引用本文复制引用
贾勇圣,张文健,刘虹麟,彭亮,杨治华,娄晋宁..KLF4对肿瘤干细胞自我更新和增殖潜能的影响[J].中国肿瘤生物治疗杂志,2011,18(4):368-372,5.基金项目
国家重点基础研究发展计划(973计划)资助项目(No.2009CB521804) （973计划）
