目的:研究INF-γ通过ATGL诱导肝癌细胞HepG2凋亡的作用及分子机制。方法:ELISA法检测血清中INF-γ水平;MTT法检测肝癌细胞HepG2活力;Caspase-3酶活性试剂盒检测Caspase-3酶活性;过表达ATGL,研究INF-γ通过ATGL诱导肝癌细胞HepG2凋亡作用。结果:肝癌病人血清中INF-γ水平明显降低(P < 0.001);INF-γ通过ATGL诱导肝癌细胞HepG2凋亡、促进Caspase-3酶活性升高和下调Bcl-2/Bax比例。结论:肝癌病人血清INF-γ水平降低,其通过下调ATGL蛋白诱导肝癌细胞HepG2凋亡。 Objective: To investigate the role and molecular mechanism of INF-gamma induced apoptosis of hepatocellular carcinoma cells (HepG2). Methods: ELISA method was used to detect the level of INF-gamma in serum. MTT assay was used to detect HepG2 proliferation, Caspase-3 enzyme activity kit was used to detect Caspase-3 enzyme activity. Overexpression of ATGL to investigate the molecular mechanism of INF-gamma induced apoptosis of hepatocellular carcinoma cells. Results: The level of INF-gamma in serum of liver cancer patients was significantly reduced. INF-gamma induced apoptosis of HepG2 cells, promoted the activity of Caspase-3 enzyme and down-regulated the proportion of Bcl-2/Bax through ATGL. Conclusion: The level of serum INF-gamma in liver cancer patients decreased and caused the apoptosis of HepG2 cells by down-regulating ATGL level.
肝癌,INF-γ,ATGL,凋亡, Liver Cancer INF-Gamma ATGL ApoptosisINF-γ通过下调ATGL蛋白水平诱导肝癌细胞HepG2凋亡
洪宏海,唐晓华,王 征,范雪娇. INF-γ通过下调ATGL蛋白水平诱导肝癌细胞HepG2凋亡 INF-Gamma Induces HepG2 Apoptosis via Down-Regulating the Level of ATGL Protein[J]. 世界肿瘤研究, 2018, 08(01): 42-48. http://dx.doi.org/10.12677/WJCR.2018.81007
参考文献 (References)ReferencesFerlay, J., et al. (2010) Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127, 2893-2917. <br>https://doi.org/10.1002/ijc.25516Venook, A.P., et al. (2010) The Incidence and Epidemiology of Hepatocellular Carcinoma: A Global and Regional Perspective. Oncologist, 154, 5-13. <br>https://doi.org/10.1634/theoncologist.2010-S4-05Altekruse, S.F., McGlynn, K.A. and Reichman, M.E. (2009) Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States from 1975 to 2005. Journal of Clinical Oncology, 27, 1485-1491.
<br>https://doi.org/10.1200/JCO.2008.20.7753Llovet, J.M., et al. (1999) Natural History of Untreated Nonsur-gical Hepatocellular Carcinoma: Rationale for the Design and Evaluation of Therapeutic Trials. Hepatology (Baltimore, MD), 29, 62-67.
<br>https://doi.org/10.1002/hep.510290145Hu, H., et al. (2017) Effects of Arsenic Trioxide on INF-gamma Gene Expression in MRL/lpr Mice and Human Lupus. Biological Trace Element Research, 1-7. <br>https://doi.org/10.1007/s12011-017-1206-9Takami, K., et al. (2002) Interferon-Gamma Inhibits Hepatocyte Growth Factor-Stimulated Cell Proliferation of Human Bronchial Epithelial Cells: Upregulation of p27kip1 Cyc-lin-Dependent Kinase Inhibitor. American Journal of Respiratory Cell and Molecular Biology, 26, 231-238. <br>https://doi.org/10.1165/ajrcmb.26.2.4643Yu, R., et al. (2014) DR4 Specific TRAIL Variants Are More Ef-ficacious than Wild-Type TRAIL in Pancreatic Cancer. Cancer Biology & Therapy, 15, 1658-1666. <br>https://doi.org/10.4161/15384047.2014.972183Willimsky, G., et al. (2008) Immunogenicity of Premalignant Lesions Is the Primary Cause of General Cytotoxic T Lymphocyte Unresponsiveness. Journal of Experimental Medicine, 205, 1687-1700.
<br>https://doi.org/10.1084/jem.20072016Lee, I., et al. (2013) Serum Interferon Gamma Level Predicts Recur-rence in Hepatocellular Carcinoma Patients after Curative Treatments. International Journal of Cancer, 133, 2895-2902. <br>https://doi.org/10.1002/ijc.28311程广霞, 等. 原发性肝癌血清细胞因子检测的临床意义[J]. 中国现代普通外科进展, 2016, 19(12): 990-991+995.Tibaldi, L., et al. (2013) New Blocking Antibodies Impede Adhesion, Migration and Survival of Ovarian Cancer Cells, Highlighting MFGE8 as a Potential Therapeutic Target of Human Ovarian Carcinoma. PLoS ONE, 8, e727088.
<br>https://doi.org/10.1371/journal.pone.0072708Grace, S.A., et al. (2017) Adipose Triglyceride Lipase (ATGL) Expression Is Associated with Adiposity and Tumor Stromal Proliferation in Patients with Pancreatic Ductal Adeno-carcinoma. Anticancer Research, 37, 699-703.
<br>https://doi.org/10.21873/anticanres.11366Bie, B., et al. (2017) Baicalein: A Review of Its Anti-Cancer Effects and Mechanisms in Hepatocellular Carcinoma. Biomedicine & Pharmacotherapy, 93, 1285-1291. <br>https://doi.org/10.1016/j.biopha.2017.07.068Bletry, O. and Papo, T. (1993) Interferons. Interferons Alpha and Gamma: Indications in Systemic Diseases. Annales de Medecine Interne, 144, 557-562.Stark, G.R. (2007) How Cells Respond to Interferons Revisited: From Early History to Current Complexity. Cytokine & Growth Factor Reviews, 18, 419-423. <br>https://doi.org/10.1016/j.cytogfr.2007.06.013李世朋, 等. 干扰素γ抑制自噬诱导肝癌HepG2细胞凋亡的作用[J]. 中国临床药理学杂志, 2017, 33(4): 343-346.Sunny, N.E., et al. (2011) Exces-sive Hepatic Mitochondrial TCA Cycle and Gluconeogenesis in Humans with Nonalcoholic Fatty Liver Disease. Cell Metabolism, 14, 804-810. <br>https://doi.org/10.1016/j.cmet.2011.11.004Savan, R. (2014) Post-Transcriptional Regulation of Interferons and Their Signaling Pathways. Journal of Interferon and Cytokine Research, 34, 318-329. <br>https://doi.org/10.1089/jir.2013.0117