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Article Open Access

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway

  • Authors:
    • Chong Li
    • Xu Zheng
    • Yanyan Han
    • Yan Lv
    • Fu Lan
    • Jie Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8973-8982
    |
    Published online on: April 13, 2018
       https://doi.org/10.3892/ol.2018.8491
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Abstract

The present study assessed the effects of the tankyrase (TNKS) small molecule inhibitor XAV939 on the proliferation and migration of lung adenocarcinoma A549 cells and the possible underlying mechanism. To do this, the association between TNKS and the WNT/β‑catenin signaling pathway in lung acinar adenocarcinoma was investigated. Immunohistochemistry was performed, which demonstrated that TNKS, β‑catenin and Myc proto‑oncogene protein (c‑Myc) proteins are positively expressed in lung adenocarcinoma tissue; this expression was significantly higher than that in normal adjacent non‑carcinoma tissues. A549 cell proliferation was inhibited in all XAV939‑intervention groups examined. In the wound‑healing assay, cells treated with different concentrations of XAV939 exhibited a significantly increased scratch width compared with the control group. Reverse transcription‑semi‑quantitative polymerase chain reaction analysis revealed that β‑catenin mRNA expression was significantly decreased in A549 cells in response to different XAV939 concentrations compared with the control group. Immunofluorescence revealed that β‑catenin protein, initially localized in the nucleus/cytoplasm, gradually translocated to the cytoplasm/membrane, an effect that was associated with increased drug concentration. TNKS, β‑catenin and c‑Myc protein expression in A549 cells treated with XAV939 was reduced compared with that in untreated cells. Therefore, abnormally high TNKS expression may promote the occurrence of lung cancer. The TNKS inhibitor XAV939 inhibited lung adenocarcinoma A549 cell proliferation and migration in vitro. The underlying mechanism by which XAV939 exerted its inhibitory effects may be associated with attenuation of the WNT signaling pathway.
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View References

1 

Zahir ST and Mirtalebi M: Survival of patients with lung cancer, Yazd, Iran. Asian Pac J Cancer Prev. 13:4387–4391. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Cancer Genome Atlas Research Networ: Comprehensive molecular profiling of lung adenocarcinoma. Nature. 511:543–550. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Liu ZL, Jin BJ, Cheng CG, Zhang FX, Wang SW, Wang Y and Wu B: Apatinib resensitizes cisplatin-resistant non-small cell lung carcinoma A549 cell through reversing multidrug resistance and suppressing ERK signaling pathway. Eur Rev Med Pharmacol Sci. 21:5370–5377. 2017.PubMed/NCBI

4 

Holland JD, Klaus A, Garratt AN and Birchmeier W: Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol. 25:855–863. 2013. View Article : Google Scholar

5 

Anastas JN and Moon RT: WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 13:11–26. 2013. View Article : Google Scholar : PubMed/NCBI

6 

McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K, Twine NC, Shie JL, Miu JT, Huang KC, et al: E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 6:41307–41323. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Busch AM, Johnson KC, Stan RV, Sanglikar A, Ahmed Y, Dmitrovsky E and Freemantle SJ: Evidence for tankyrases as antineoplastic targets in lung cancer. Bmc Cancer. 13:2112013. View Article : Google Scholar : PubMed/NCBI

8 

Kulak O, Chen H, Holohan B, Wu X, He H, Borek D, Otwinowski Z, Yamaguchi K, Garofalo LA, Ma Z, et al: Disruption of Wnt/β-catenin signaling and telomeric shortening are inextricable consequences of tankyrase inhibition in human cells. Mol Cell Biol. 35:2425–2435. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Wang C, Zhu H, Sun Z, Xiang Z, Ge Y, Ni C, Luo Z, Qian W and Han X: Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury. Am J Physiol Cell Physiol. 307:C234–C244. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Kamal A, Riyaz S, Srivastava AK and Rahim A: Tankyrase inhibitors as therapeutic targets for cancer. Curr Top Med Chem. 14:1967–1976. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Casás-Selves M, Kim J, Zhang Z, Helfrich BA, Gao D, Porter CC, Scarborough HA, Bunn PA Jr, Chan DC, Tan AC and DeGregori J: Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Res. 72:4154–4164. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Arqués O, Chicote I, Puig I, Tenbaum SP, Argilés G, Dienstmann R, Fernández N, Caratù G, Matito J, Silberschmidt D, et al: Tankyrase inhibition blocks Wnt/β-catenin pathway and reverts resistance to PI3K and AKT inhibitors in the treatment of colorectal cancer. Clin Cancer Res. 22:644–656. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Voronkov A and Krauss S: Wnt/beta-catenin signaling and small molecule inhibitors. Curr Pharm Des. 19:634–664. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Polakis P: Drugging Wnt signalling in cancer. EMBO J. 31:2737–2746. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, et al: Tankyrase inhibition stabilizes axin and antagonizes WNT signaling. Nature. 461:614–620. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Wu X, Luo F, Li J, Zhong X and Liu K: Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. Int J Oncol. 48:1333–1340. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Clevers H and Nusse R: Wnt/β-catenin signaling and disease. Cell. 149:1192–1205. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Lecarpentier Y, Claes V, Duthoit G and Hébert JL: Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction. Front Physiol. 5:4292014. View Article : Google Scholar : PubMed/NCBI

20 

Dregalla RC, Zhou J, Idate RR, Battaglia CL, Liber HL and Bailey SM: Regulatory roles of tankyrase 1 at telomeres and in DNA repair: Suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany NY). 2:691–708. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Tian XH, Hou WJ, Yan F, Fan J, Tong H, Bai SL, Chen Q, Xu H and Li Y: XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res. 32:1002013. View Article : Google Scholar : PubMed/NCBI

22 

de la Roche M, Ibrahim AE, Mieszczanek J and Bienz M: LEF1 and B9L shield β-catenin from inactivation by Axin, desensitizing colorectal cancer cells to tankyrase inhibitors. Cancer Res. 74:1495–1505. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Chen X, Meng J, Yue W, Yu J, Yang J, Yao Z and Zhang L: Fibulin-3 suppresses Wnt/β-catenin signaling and lung cancer invasion. Carcinogenesis. 35:1707–1716. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Lim JH, Park JW and Chun YS: Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation. Cancer Res. 66:10677–10682. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Zhang X, Lou Y, Zheng X, Wang H, Sun J, Dong Q and Han B: Wnt blockers inhibit the proliferation of lung cancer stem cells. Drug Des Devel Ther. 9:2399–2407. 2015.PubMed/NCBI

26 

Thorvaldsen TE, Pedersen NM, Wenzel EM, Schultz SW, Brech A, Liestøl K, Waaler J, Krauss S and Stenmark H: Structure, dynamics and functionality of tankyrase inhibitor-induced degradasomes. Mol Cancer Res. 13:1487–1501. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Krishnamurthy N and Kurzrock R: Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 62:50–60. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Zhang X, Lou Y, Zheng X, Wang H, Sun J, Dong Q and Han B: Wnt blockers inhibit the proliferation of lung cancer stem cells. Drug Des Devel Ther. 9:2399–2407. 2015.PubMed/NCBI

29 

Kahn M: Can we safely target the WNT pathway? Nat Rev Drug Discov. 13:513–532. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Riffell JL, Lord CJ and Ashworth A: Tankyrase-targeted therapeutics: Expanding opportunities in the PARP family. Nat Rev Drug Discov. 11:923–936. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li C, Zheng X, Han Y, Lv Y, Lan F and Zhao J: XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncol Lett 15: 8973-8982, 2018.
APA
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., & Zhao, J. (2018). XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncology Letters, 15, 8973-8982. https://doi.org/10.3892/ol.2018.8491
MLA
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., Zhao, J."XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway". Oncology Letters 15.6 (2018): 8973-8982.
Chicago
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., Zhao, J."XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway". Oncology Letters 15, no. 6 (2018): 8973-8982. https://doi.org/10.3892/ol.2018.8491
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Zheng X, Han Y, Lv Y, Lan F and Zhao J: XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncol Lett 15: 8973-8982, 2018.
APA
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., & Zhao, J. (2018). XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway. Oncology Letters, 15, 8973-8982. https://doi.org/10.3892/ol.2018.8491
MLA
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., Zhao, J."XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway". Oncology Letters 15.6 (2018): 8973-8982.
Chicago
Li, C., Zheng, X., Han, Y., Lv, Y., Lan, F., Zhao, J."XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway". Oncology Letters 15, no. 6 (2018): 8973-8982. https://doi.org/10.3892/ol.2018.8491
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