Chen T, Xiong J, Yang C, Shan L, Tan G, Yu L, Tan Y
State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, China.
Cancer Gene Ther. 2014 Mar;21(3):133-8. doi: 10.1038/cgt.2014.8. Epub 2014 Feb 28.
The Forkhead Box M1 (FOXM1) transcription factor has been considered as a potential target for the prevention and/or therapeutic intervention in human carcinomas because of its roles in tumorigenesis and tumor progression through regulating the expression of genes relevant to cell proliferation and transformation. In this study, FOXM1 was found to express strongly in both clinical tissue specimens and human hepatocellular carcinoma (HCC) cell lines such as Huh-6, Huh-7 and HepG2. The knockdown of FOXM1 expression through an adenovirus vector (named AdFOXM1shRNA), which expresses a short hairpin RNA to downregulate FOXM1 expression specifically, diminished the proliferation of Huh-7 and HepG2 cells and anchorage-independent growth of Huh-7 cells. Furthermore, we assessed the efficacy of AdFOXM1shRNA for tumor gene therapy with the Huh-7 cell xenograft mouse model and found that the tumor growth was significantly suppressed when inoculated mice were injected with AdFOXM1shRNA in the tumors. Together, our results suggest that FOXM1 is a potential therapeutic target for HCC and AdFOXM1shRNA may be an additional gene therapeutic intervention for HCC treatment.
叉头框M1（FOXM1）转录因子因其通过调控与细胞增殖和转化相关基因的表达，在肿瘤发生和肿瘤进展中发挥作用，而被视为人类癌症预防和/或治疗干预的潜在靶点。在本研究中，发现FOXM1在临床组织标本和人肝癌（HCC）细胞系如Huh-6、Huh-7和HepG2中均强烈表达。通过腺病毒载体（命名为AdFOXM1shRNA）敲低FOXM1表达，该载体表达短发夹RNA以特异性下调FOXM1表达，可减少Huh-7和HepG2细胞的增殖以及Huh-7细胞的非锚定依赖性生长。此外，我们用Huh-7细胞异种移植小鼠模型评估了AdFOXM1shRNA用于肿瘤基因治疗的疗效，发现当给接种小鼠的肿瘤注射AdFOXM1shRNA时，肿瘤生长受到显著抑制。总之，我们的结果表明FOXM1是HCC的潜在治疗靶点，AdFOXM1shRNA可能是HCC治疗的另一种基因治疗干预手段。
