NFAT2在原发性肝癌中的表达及对肝癌细胞增殖及凋亡的影响

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摘要目的: 探讨激活的T细胞核因子2(nuclear factor of activated T cells 2, NFAT2)在原发性肝癌中表达及对肝癌细胞增殖及凋亡影响。方法: 选取40例肝癌患者，取其癌组织与癌旁组织，蛋白质印迹检测NFAT2蛋白表达；构建NFAT2过表达质粒并转染肝癌细胞Huh7和PLC，通过CCK8方法和克隆形成实验检测肝癌细胞增殖能力，流式细胞术检测肝癌细胞凋亡，蛋白质印迹检测相关凋亡蛋白表达。结果： NFAT2在肝癌组织中的表达明显低于癌旁组织(P<0.05)；NFAT2质粒转染细胞后，肝癌细胞增殖率明显降低(P<0.01)，克隆形成数明显减少(P<0.05)，凋亡率明显增加(P<0.05)，相关凋亡蛋白Caspase8及Caspase3表达增加。结论：肝癌组织中NFAT2的表达明显下降，NFAT2过表达可抑制肝癌细胞增殖并促进其凋亡。

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关键词 ：肝癌, 激活的T细胞核因子2, 增殖, 凋亡

Abstract：Objective: To investigate the expression of the nuclear factor of activated T cells 2(NFAT2) in primary hepatocellular carcinoma(HCC) tissues and its effect on the proliferation and apoptosis of HCC cells. Methods: Total protein was extracted from the cancer and adjacent noncancerous liver tissues from 40 HCC patients and the expression of NFAT2 protein was detected by Western blotting. NFAT2 overexpression plasmid was constructed and was transfected into HCC cell lines Huh7 and PLC. We used CCK8 assay and cell colony formation assay to evaluate the HCC cell proliferation, flow cytometry to evaluate HCC apoptosis and Western blotting to examine apoptosis related proteins. Results: The expression of NFAT2 in HCC tissues was significantly lower than that in the adjacent noncancerous liver tissues(P<0.05). After cells were transfected with NFAT2 plasmid, cell proliferation rate and colony formation number significantly decreased(P<0.05), but apoptosis rate significantly increased(P<0.01), the expression of the apoptosisrelated protein cleaved Caspase8 and cleaved Caspase3 was increased. Conclusion: NFAT2 expression in HCC tissues decreased significantly; overexpression of NFAT2 could reduce cell proliferation and promote cell apoptosis.

收稿日期: 2017-03-13

基金资助:

国家自然科学基金资助项目(81301693)；江苏省自然科学基金资助项目(BK20130474)；镇江市社会发展项目(SH2013032)；江苏省研究生创新项目(1201270052)

通讯作者: 张进(通讯作者)，主治医师，博士，E-mail: 8093519@qq.com

作者简介: 徐三荣(1963—)，博士，主任医师，硕士生导师，主要从事肝胆胰脾外科研究

引用本文:

徐三荣，束鹏浩，张勇，张进. NFAT2在原发性肝癌中的表达及对肝癌细胞增殖及凋亡的影响[J]. 江苏大学学报:医学版, 2017, 27(02): 98-102. XU San-rong, SHU Peng-hao, ZHANG Yong, ZHANG Jin. Expression of NFAT2 in hepatocellular carcinoma and its effect on proliferation and apoptosis of hepatocellular carcinoma cells. Journal of Jiangsu University(Medicine Edition), 2017, 27(02): 98-102.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2017/V27/I02/98

[1\]Yang G, Chang B, Yang F, et al. Aurora kinase A promotes ovarian tumorigenesis through dysregulation of the cell cycle and suppression of BRCA2\[J\]. Clin Cancer Res, 2010,16(12):3171-3181.
\[2\]杨璟, 陈建平, 徐斌, 等. 果糖1,6二磷酸酶在肝癌组织的表达及其对预后的影响\[J\]. 中华实验外科杂志, 2016,33(4):1088-1090.
\[3\]Shaw JP, Utz PJ, Durand DB, et al. Identification of a putative regulator of early T cell activation genes\[J\]. Science, 1988,241(4862): 202-205.
\[4\]Ohhora M,Rao A.The calcium/NFAT pathway: role in development and function of regulatory T cells\[J\]. Microbes Infect, 2009, 11(5):612-619.
\[5\]赵宏, 赵守华. 活化T细胞核因子与肿瘤的研究进展\[J\]. 中华临床医师杂志(电子版), 2014,8(14):2696-2700.
\[6\]张悦, 梁春立. NFAT分子在肿瘤发生与发展中的作用\[J\]. 中国肿瘤生物治疗杂志, 2010,17(3):344-348.
\[7\]Li R,Zhang L,Shi W,et al.NFAT2 mediates high glucoseinduced glomerular podocyte apoptosis through increased Bax expression\[J\].Exp Cell Res, 2013, 319(7):922-1000.
\[8\]Chai WR, Wang Q, Gao HB. NFAT2 is implicated in corticosteroneinduced rat Leydig cell apoptosis\[J\]. Asian J Androl, 2007, 9(5):623-633.
\[9\]张进, 刘志苏, 刘权焰, 等. 激活的T细胞核因子家族在肝癌与癌旁组织中的差异表达\[J\]. 中华实验外科杂志, 2012,29(2):237-239.
\[10\]章志坚, 韩少良, 朱冠保. 抑癌基因KAI1/CD82异常表达与胃肠道肿瘤发生发展\[J\]. 医学综述, 2008,14(2):215-217.
\[11\]董博文, 郑桐森, 代文杰. 肿瘤发生发展与FEZ1/LZTS1关系的研究进展\[J\]. 中华实验外科杂志, 2011, 28(1):157-158.
\[12\]FoldynovTrantírkov S, Sekyrov P, Tmejov K, et al. Breast cancerspecific mutations in CK1ε inhibit Wnt/βcatenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration\[J\]. Breast Cancer Res, 2010,12(3):R30.
\[13\]Yissachar N, Sharar Fischler T, Cohen AA, et al. Dynamic response diversity of NFAT isoforms in individual living cells\[J\]. Mol Cell, 2013, 49(2):322-330.
\[14\]Marafioti T, Pozzobon M, Hansmann ML, et al. The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas\[J\]. Br J Haematol, 2005, 128(3):333-342.
\[15\]Lawrence MC, Naziruddin B, Levy MF, et al. Calcineurin/nuclear factor of activated T cells and MAPK signaling induce TNFα gene expression in pancreatic islet endocrine cells\[J\]. J Biol Chem, 2011, 286(2):1025-1036.
\[16\]Orhue V, Kanaji A, Caicedo MS, et al. Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobaltchromiummolybdenum(CoCrMo) particlesinduced tumor necrosis factorα(TNFα) secretion in MLOY4 osteocytes\[J\]. J Orthop Res, 2011, 29(12):1867-1873.
\[17\]Mancini M, Toker A. NFAT proteins: emerging roles in cancer progression\[J\]. Nat Rev Cancer, 2009, 9(11): 810-820.
\[18\]Qin JJ, Nag S, Wang W, et al. NFAT as cancer target: mission possible?\[J\]. Biochim Biophys Acta, 2014,1846(2):297-311.
\[19\]Horsley V, Aliprantis AO, Polak L, et al. NFATc1 balances quiescence and proliferation of skin stem cells\[J\]. Cell, 2008, 132(2): 299-310.
\[20\]Zhou B, Cron RQ, Wu B, et al. Regulation of the murine Nfatc1 gene by NFATc2\[J\]. J Biol Chem, 2002, 277(12):10704-10711.
\[21\]Müller MR, Rao A. NFAT, immunity and cancer: a transcription factor comes of age\[J\]. Nat Rev Immunol, 2010, 10(9):645-656.
\[22\]Vaeth M, Müller G, Stauss D, et al. Follicular regulatory T cells control humoral autoimmunity via NFAT2regulated CXCR5 expression\[J\]. J Exp Med, 2014, 211(3): 545-561.
\[23\]Lee YS, Kim DW, Kim S, et al. Downregulation of NFAT2 promotes melanogenesis in B16 melanoma cells\[J\]. Anat Cell Biol, 2010, 43(4): 303-309.
\[24\]Lucena PI, Faget DV, Pachulec E, et al. NFAT2 isoforms differentially regulate gene expression, cell death, and transformation through alternative Nterminal domains\[J\]. Mol Cell Biol, 2016, 36(1):119-131.