ABL2在肺癌中的作用及机制研究

doi:10.11904/j.issn.1002-3070.2019.06.004

摘要/Abstract

摘要： 目的探究ABL2在肺癌中的作用及其机制。方法采用Realtime PCR方法检测ABL2在肺癌组织和癌旁组织中的表达情况。然后建立稳定低表达ABL2的肺腺癌A549细胞株;通过MTT、细胞迁移和克隆形成实验检测细胞增殖和迁移能力的变化情况;Western blot检测EMT、凋亡和PI3K/AKT信号通路相关蛋白的表达情况。结果肺癌组织中ABL2的表达水平明显高于癌旁组织(P＜0.001)。在A549细胞系中沉默ABL2后,与对照组相比,48 h后细胞的迁移能力减弱(P＜0.001),从第3天开始细胞的生长速度开始明显减缓(P＜0.05),15天后形成的平均克隆数也减少(P＜0.01)。Western blot结果显示,沉默ABL2后上皮细胞标志物E-cadherin表达升高(P＜0.001),间质细胞标志物N-cadherin(P＜0.001)、Vimentin(P＜0.01)及Snail(P＜0.001)表达降低。凋亡相关蛋白Bcl-XL表达下降(P＜0.01),BAX表达上调(P＜0.001)。PI3K/AKT信号通路相关蛋白PI3K P110(P＜0.05)、AKT(P＜0.01)和p-AKT(P＜0.05)蛋白的表达都明显降低。结论沉默ABL2基因能够通过PI3K/AKT信号通路促进细胞凋亡,抑制肺癌细胞的增殖和迁移。

关键词: 肺癌, ABL2, 凋亡

Abstract: Objective The aim of this study was to investigate the role and mechanism of ABL2 in lung cancer and its mechanism.Methods The expression of ABL2 in lung cancer and adjacent tissues was detected by Real-Time PCR.A lung adenocarcinoma A549 cell line stably expressing of ABL2 was established,and the changes of cell proliferation and migration ability were detected by MTT,cell migration and colony formation assays.Western blot was used to detect the expression of EMT,apoptosis and PI3K/AKT signaling pathway-related proteins.Results The expression of ABL2 in lung cancer tissues was significantly higher than that in adjacent tissues(P＜0.001).After silencing ABL2 in the A549 cells,compared with the control group,the migration ability of cells was weakened after 48 hours(P＜0.001),the growth rate of cells began to slow down from the third day(P＜0.05),and the average number of clones formed after 15 days also decreased(P＜0.01).The expression of E-cadherin(P＜0.001)was increased in the epithelial cell marker after silencing ABL2,and the expression of stromal cell markers N-cadherin(P＜0.001),Vimentin(P＜0.01)and Snail(P＜0.001)was decreased.The expression of apoptosis-related protein Bcl-XL(P＜0.01)was decreased and BAX(P＜0.001)expression was up-regulated.The expression of PI3K/AKT signaling pathway-associated proteins such as PI3K P110(P＜0.05),AKT(P＜0.01)and p-AKT(P＜0.05)was significantly decreased.Conclusion Silencing ABL2 gene can promote apoptosis,and inhibit proliferation and migration of lung cancer cells through a PI3K/AKT signaling pathway.

Key words: Lung cancer, ABL2, Apoptosis

中图分类号:

R734.2

李传海, 刘玉, 王延群, 陈英剑. ABL2在肺癌中的作用及机制研究[J]. 实用肿瘤学杂志, 2019, 33(6): 497-501.

LI Chuanhai, LIU Yu, WANG Yanqun, CHEN Yingjian. The role and mechanism of ABL2 in lung cancer[J]. Journal of Practical Oncology, 2019, 33(6): 497-501.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2019.06.004

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2019/V33/I6/497

参考文献

1 Wang J,Pendergast AM.The emerging role of ABL kinases in solid tumors[J].Trends Cancer,2015,1(2):110-123.
2 Bronte F,Bronte E,Bronte G,et al.Targeted therapies in hepatocellular carcinoma[J].Curr Med Chem,2014,21(8):966-974.
3 Kazi JU,Rupar K,Marhäll A,et al.ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling[J].Oncotarget,2017,8(7):12194-12202.
4 Zhang K,Lyu W,Yu J,et al.ABL2 is recruited to ventral actin waves through cytoskeletal interactions to promote lamellipodium extension[J].Mol Biol Cell,2018,29(23):2863-2873.
5 Xue M,Qin X,Wan Y,et al.MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2[J].Drug Des Devel Ther,2015,10:71-79.
6 Wang J,Pendergast AM.The emerging role of ABL kinases in solid tumors[J].Trends Cancer,2015,1(2):110-123.
7 Ganguly SS,Fiore LS,Sims JT,et al.c-Abl and Arg are activated in human primary melanomas,promote melanoma cell invasion via distinct pathways,and drive metastatic progression[J].Oncogene,2012,31(14):1804-1816.
8 Srinivasan D.Activation of Abl tyrosine kinases promotes invasion of aggressive breast cancer cells[J].Cancer Res,2006,66(11):5648-5655.
9 Mader CC,Oser M,Magalhaes MA,et al.An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion[J].Cancer Res,2011,71(5):1730-1741.
10 Gu JJ,Rouse C,Xu X,et al.Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis[J].Jci Insight,2016,1(21):89647.
11 Bianchi C,Torsello B,Di Stefano V,et al.One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology,motility and the cytoskeleton[J].Exp Cell Res,2013,319(13):2091-2102.
12 Xing QT,Qu CM,Wang G.Overexpression of ABL2 predicts poor prognosis in hepatocellular carcinomas and is associated with cancer cell migration and invasion[J].Onco Targets Ther,2014,7:881-885.
13 Ganguly SS,Fiore LS,Sims JT,et al.c-ABL and Arg are activated in human primary melanomas,promote melanoma cell invasion via distinct pathways,and drive metastatic progression[J].Oncogene,2012,31(14):1804-1816.
14 Sami A,Karsy M.Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma:novel therapeutic agents and advances in understanding[J].Tumor Biol,2013,34(4):1991-2002.
15 Huilin G,Pengbiao L,Jiangwei Z,et al.Na+/K+-ATPase DR region-specific antibody protects U251 cells against hypoxia reperfusion-induced injury via the PI3K/AKT and ERK pathways[J].Mol Med Rep,2017,16(6):7901-7906.
16 Kwon CH,Park HJ,Choi Y,et al.TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells[J].Tumor Biol,2017,39(10):101042831772207.
17 Dhivya R,Ranjani J,Bowen PK,et al.Biocompatible curcumin loaded PMMA-PEG/ZnO nanocomposite induce apoptosis and cytotoxicity in human gastric cancer cells[J].Mater Sci Eng C Mater Biol Appl,2017,80:59.
18 桂律,林梅绥.凋亡抑制基因bcl-2,p53及ki-67在膀胱良恶性病变中的表达[J].实用肿瘤学杂志,2000,14(3):177-179.

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