目的 探讨ADAM-17抑制剂TNF484对肝癌细胞增殖、迁移和侵袭的影响。 方法 选用肝癌HepG2细胞株和Bel7402细胞作为研究对象,分为TNF484抑制组及空白对照组,利用MTT法检测TNF 484对两种肝癌细胞株增殖影响,用PCR法检测TNF 484对肝癌细胞ADAM-17表达的影响,利用迁移分析及细胞侵袭实验分析TNF 484对肝癌细胞迁移和侵袭能力的影响。 结果 TNF484可以显著抑制肿瘤细胞生长,呈剂量依赖性,100 μM 时对HepG2和Bel7402细胞株增殖抑制作用最大,抑制率分别为(80±5.6)%和(85±5.8)%;10 μM作用72 h,HepG2和BEL7402细胞株的空白对照组及抑制组的细胞分数分别为(80.92%±6.10%、55.60%±4.21%)、(82.62%±6.15%、59.8%±4.27%),两组比较差异均有统计学意义(P<0.05);同时10 μM TNF484作用 72 h后HepG2及BEL-7402细胞株中ADAM-17RNA表达水平降低,抑制率分别为(45±3.1)%及(48±3.3)%。 结论 ADAM-17抑制剂TNF484对肝癌细胞增殖、迁移和侵袭有明显抑制作用,ADAM-17可能是HCC基因治疗的有效靶目标。
Abstract
Objective To investigate the effect of ADAM-17 inhibitor TNF484 on proliferation, migration and invasion of hepatocellular carcinoma cells.Methods Hepatoma HepG2 cell line and Bel7402 cell line were selected as the subjects, which were divided into the TNF484 inhibition group and blank control group. MTT assay was used to detect the effect of TNF 484 on the proliferation of two hepatocellular carcinoma cell lines. PCR was used to detect the effect of TNF 484 on the expression of ADAM-17 hepatocellular carcinoma cells. The effect of TNF-484 on the migration and invasion of hepatocellular carcinoma cells was analyzed using migration analysis and cell invasion assays.Results TNF484 significantly inhibited the growth of tumor cells in a dose-dependent manner. The inhibition of HepG2 and Bel7402 cell proliferation reached the peak at 100 μM, and the inhibition rates were (80±5.6)% and (85±5.8)%, respectively. The cell fractions of of HepG2 and BEL 7402 cell lines in the blank control group and the inhibition group were (80.92±6.10, 55.60±4.21) and (82.62±6.15, 59.8±4.27) respectively at 10 μM for 72 h. At the same time, the expression of ADAM-17 RNA in HepG2 and BEL-7402 cell lines was decreased after ten hours of TNF 484 treatment, and the inhibition rates were(45±3.1)% and (48±3.3)%, respectively.Conclusions The ADAM-17 inhibitor TNF484 can significantly inhibit the proliferation, migration and invasion of hepatoma cells. Therefore, ADAM-17 is expected to become a new target for clinical observation and treatment.
关键词
ADAM-17 /
TNF484 /
肝细胞癌
Key words
ADAM-17 /
TNF484 /
hepatocellular carcinoma
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] El-Serag H B. Hepatocellular carcinoma [J]. N Engl J Med, 2011, 365(12): 1118-1127.
[2] Jemal A, Bray F, Center M M, et al. Global cancer statistics [J]. CA Cancer J Clin, 2011, 61(2): 69-90.
[3] Van Schaeybroeck S, Kyula J N, Fenton A, et al. Oncogenic Kras promotes chemotherapy -induced growth factor shedding via ADAM17 [J]. Cancer Res, 2011, 71(3): 1071-1080.
[4] Allinson T M, Parkin E T, Turner A J, et al. ADAMs family members as amyloid precursor protein alpha-secretases[J]. J Neurosci Res, 2003, 74(3): 342-352.
[5] Benarroch E E. ADAM protenins, their ligands,and clinical implications [J]. Neurology, 2012, 78(12): 914-920.
[6] Scheller J, Chalaris A, Garbers C, et al. ADAM 17: a molecular switch to control inflammation and tissue regeneration [J]. Trends Immunol, 2011, 32(8): 380-387.
[7] Stanton H, Melrose J, Little C B, et al. Proteoglycan degradation by the ADAMTS family of proteinases [J]. Bioehim Biophys Acta, 2011, 1812(12): 1616-1629.
[8] Katakowski M, Jiang F, Zheng X, et al. Tumorigenicity of cortical astrocyte cell line induced by the protease ADAM17 [J]. Cancer Sci, 2009, 100(9): 1597-1604.
[9] Zheng X, Jiang F, Katakowski M, et al. ADAMl7 promotes glioma cell malignant phenotype [J]. Mol Carcinog, 2012, 51(2): 150-164.
[10] Baumgart A, Seidl S, Vlachou P, et al. ADAM17 regulates epidermal growth factor receptor expression through the activafion of Notchl in non-small cell lung cancer [J]. Cancer Res, 2010, 70(13): 5368-5378.
[11] Narita D, Seclarnan E, Ursoniu S, et al. Increased expression of ADAM 12 and ADAM 17 genes in laser-capture microdissected breast cancel s and correlations with clinical and pathological characteristics [J]. Acta Histochem, 2012, l14(2): 131-139.
[12] Sinnathamby G, Zeffass J, Hafner J, et al. ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeufic target in breast, ovarian and prostate cancers [J]. Clin Exp Immunol, 2011, 163(3): 324-332.
[13] Merchant N B, Voskresensky I, Rogers C M, et al. TACE/ADAM-17: a component of the epidermal growth factor receptor axis and a promising therapeutic target in colorectal cancer [J]. J Clin Cancer Res, 2008, 14(4): 1182-1191.
[14] 刘 爽,马 荣. ADAM-17在恶性肿瘤中的研究及其进展[J].现代生物医学进展, 2016, 13(17):3386-3389.
基金
吴阶平医学基金会临床科研专项(320.6750.17081)
PDF(794 KB)
