[1]王晓,黄晓平,刁勇.TRAIL与kallistatin联合表达载体的构建及抗肿瘤活性分析[J].华侨大学学报(自然科学版),2021,42(3):378-383.[doi:10.11830/ISSN.1000-5013.202008020]
　WANG Xiao,HUANG Xiaoping,DIAO Yong.Construction of TRAIL and Kallistatin Combined Expression Vector and Its Antitumor Activity Analysis[J].Journal of Huaqiao University(Natural Science),2021,42(3):378-383.[doi:10.11830/ISSN.1000-5013.202008020]
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TRAIL与kallistatin联合表达载体的构建及抗肿瘤活性分析()
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《华侨大学学报（自然科学版）》[ISSN:1000-5013/CN:35-1079/N]

卷:
第42卷
期数:
2021年第3期
页码:
378-383
栏目:
出版日期:
2021-05-20

文章信息/Info

Title:
Construction of TRAIL and Kallistatin Combined Expression Vector and Its Antitumor Activity Analysis
文章编号:
1000-5013(2021)03-0378-06
作者:
王晓1; 2;  黄晓平1; 2;  刁勇1; 2
1. 华侨大学 医学院, 福建 泉州 362021; 2. 华侨大学 生物医学学院, 福建 泉州 362021
Author(s):
WANG Xiao1; 2;  HUANG Xiaoping1; 2;  DIAO Yong1; 2
1. School of Medical, Huaqiao University, Quanzhou 362021, China; 2. School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China
关键词:
抗肿瘤;  组织激肽释放酶结合蛋白;  肿瘤坏死因子相关凋亡诱导配体;  细胞凋亡
Keywords:
antitumor;  kallistatin;  tumor necrosis factor-related apoptosis-inducing ligand;  apoptosis
分类号:
R730.54
DOI:
10.11830/ISSN.1000-5013.202008020
文献标志码:
A
摘要:
为研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)与组织激肽释放酶结合蛋白(kallistatin)联合用药的抗肿瘤作用,构建TRAIL与kallistatin双表达的重组质粒pAM-CAG-Kal-IRES-TRAIL,将重组质粒转染A549,LO-2,NCI-H446和Hela细胞,考察其抗肿瘤活性.实验结果表明:构建的双表达载体能同时表达TRAIL与kallistatin,且均能分泌至培养基中;TRAIL与kallistatin联合表达对肿瘤细胞活力的抑制作用明显增强,诱导肿瘤凋亡的作用也明显增强,说明联合表达TRAIL与kallistatin能够增强抗肿瘤活性.
Abstract:
In order to study the anti-tumor effect of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)combined with kallistatin, a dual-expression of TRAIL and kallistatin recombinant plasmid pAM-CAG-Kal-IRES-TRAIL was constructed and then transfected into A549, LO-2, NCI-H446 and Hela cells with liposome to investigate the anti-tumor activity of the dual expression vector. The experimental results show that the constructed dual expression vector can express TRAIL and kallistatin simultaneously, and both of these proteins can be secreted into the culture medium; the combination of TRAIL and kallistatin expression significantly enhances the inhibition of tumor cells viability and induces apoptosis of tumor cells, which indicates that the combined expression of TRAIL and kallistatin can enhance anti-tumor activity.

参考文献/References:

[1] LEMKE J,VON KARSTEDT S,ZINNGREBE J,et al.Getting TRAIL back on track for cancer therapy[J].Cell Death and Differentiation,2014,21(9):1350-1364.DOI:10.1038/cdd.2014.81.
[2] 张均平,刘会杰,杨洋,等.(R)-Preconviction诱导Hela细胞凋亡的分子机制[J].华侨大学学报(自然科学版),2013,34(4):422-428.DOI:10.11830/ISSN.1000-5013.2013.04.0422.
[3] DIMBERG L Y,ANDERSON C K,CAMIDGE R,et al.On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics[J].Oncogene,2013,32(11):1341-1350.DOI:10.1038/ONC.2012.164.
[4] SO J,PASCULESCU A,DAI A,et al.Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy[J].Science Signaling,2015,8(371):1-18.DOI:10.1126/SCISIGNAL.2005700.
[5] HUANG Kaifei,YANG Huiyong,XING Yongmei,et al.Recombinant human kallistatin inhibits angiogenesis by blocking VEGF signaling pathway[J].Journal of Cellular Biochemistry,2014,115(3):575-584.DOI:10.1002/JCB.24693.
[6] LI Pengfei,GUO Youming,BLEDSOE G,et al.Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis[J].Experimental Cell Research,2016,340(2):305-314.DOI:10.1016/J.YEXCR.2016.01.004.
[7] SENO M,HINUMA S,ONDA H,et al.A hybrid protein between IFN-gamma and IL-2[J].FEBS Letters,1986,199(2):187-192.DOI:10.1016/0014-5793(86)80477-X.
[8] 王启钊,吕颖慧,费凌娜,等.肿瘤基因治疗的研究进展与思考[J].中国肿瘤临床,2020,37(15):893-896.DOI:10.3969/J.ISSN.1000-8179.2010.15.015.
[9] CHOI C,KUTSCH O,PARK J,et al.Tumor necrosis factor-related apoptosis-inducing ligand induces caspase-dependent interleukin-8 expression and apoptosis in human astroglioma cells[J].Molecular and Cellular Biology,2002,22(3):724-736.DOI:10.1128/MCB.22.3.724-736.2002.
[10] WALCZAK H,HAAS T L.Biochemical analysis of the native TRAIL death-inducing signaling complex[J].Methods in Molecular Biology,2008,414:221-239.DOI:10.1007/978-1-59745-339-4_16.
[11] GENG Chuanying,HOU Jian,ZHAO Yaozhong,et al.A multicenter, open-label phase Ⅱ study of recombinant CPT(Circularly Permuted TRAIL)plus thalidomide in patients with relapsed and refractory multiple myeloma[J].American Journal of Hematology,2014,89(11):1037-1042.DOI:10.1002/AJH.23822.
[12] 朱玲,王祥喜,李雪梅,等.TRAIL诱导肿瘤细胞凋亡的分子机制及其在肿瘤生物治疗中的应用前景[J].生物物理学报,2012,28(6):448-456.DOI:10.3724/SP.J.1260.2012.20047.
[13] HUANG Kaifei,HUANG Xiaoping,DIAO Yong,et al.Kallistatin, a novel anti-angiogenesis agent, inhibits angiogenesis via inhibition of the NF-κB signaling pathway[J].Biomedicine and Pharmacotherapy,2014,68(4):455-461.DOI:10.1016/J.BIOPHA.2014.03.005.
[14] HUANG Xiaoping,WANG Xiao,XIE Xiaolan,et al.Cell surface expression of nucleolin mediates the antiangiogenic and antitumor activities of kallistatin[J].Oncotarget,2018,9(2):2220-2235.DOI:10.18632/ONCOTARGET.23346.
[15] WANG Guoquan,WANG Xiao,HUANG Xiaoping,et al.Inhibition of integrin beta3, a binding partner of kallistatin, leads to reduced viability, invasion and proliferation in NCI-H446 cells[J].Cancer Cell International,2016,16:90.DOI:10.1186/S12935-016-0365-7.
[16] PONNAZHAGAN S,MAHENDRA G,KUMAR S,et al.Adeno-associated virus 2-mediated antiangiogenic cancer gene therapy: Long-term efficacy of a vector encoding angiostatin and endostatin over vectors encoding a single factor[J].Cancer Research,2004,64(5):1781-1787.DOI:10.1158/0008-5472.can-03-1786.

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备注/Memo

备注/Memo:
收稿日期: 2020-08-16
通信作者: 刁勇(1967-),男,教授,博士,博士生导师,主要从事新药研发、基因药物的研究.E-mail:diaoyong@hqu.edu.cn.
基金项目: 国家自然科学基金资助项目(81371669); 福建省自然科学基金资助项目(2017J01548); 福建省泉州市科技项目(2020C061, 2016N070); 华侨大学科研基金资助项目(17BS501)
更新日期/Last Update: 2021-05-20