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Article

Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3

  • Authors:
    • Jie Tang
    • Fuchun Guo
    • Yang Du
    • Xiaoling Liu
    • Qing Qin
    • Xiaoke Liu
    • Tao Yin
    • Li Jiang
    • Yongsheng Wang
  • View Affiliations / Copyright

    Affiliations: Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospita, Chengdu, Sichuan 610041, P.R. China, Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospita, Chengdu, Sichuan 610041, P.R. China, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, P.R. China
  • Pages: 2083-2095
    |
    Published online on: February 17, 2015
       https://doi.org/10.3892/ijo.2015.2898
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Abstract

Epidermal growth factor receptor‑tyrosine kinase inhibitors (EGFR‑TKIs) have shown promising effects against the growth of non‑small cell lung cancer (NSCLC) cells harboring EGFR mutations (EGFR‑mts). However, many patients with NSCLC that are accepted for EGFR‑TKI treatment followed by chemotherapy possess an unknown EGFR status including wild‑type EGFR (EGFR‑wt). Little is known about the potential effects of EGFR‑TKI treatment prior to chemotherapy. We investigated the effects and underlying molecular events of 4 weeks of continuous exposure to EGFR‑TKIs in the EGFR‑wt NSCLC line H1299. This treatment dramatically increased the IC50 of several relevant chemotherapeutic agents: cisplatin (DDP) (29.25±6.1 µM for gefitinib, 43.25±14.87 µM for erlotinib, and 6.92±1.15 µM for parental), paclitaxel (11.16±3.36 µM for gefitinib, 9.16±1.41 µM for erlotinib, and 2.09±0.44 µM for parental), gemcitabine (47.18±6.2 µM for gefitinib, 40.36±11.1 µM for erlotinib, and 16.00±3.38 µM for parental) and pemetrexed (11.78±4.07 µM for gefitinib, 15.97±7.23 µM for erlotinib, and 4.72±1.9 µM for parental). This chemoresistance was critically dependent on the activation of the mediator signal transducer and activator of transcription 3 (STAT3). In cells exposed to EGFR‑TKIs for 4 weeks, activation of STAT3 was found to be unrelated to EGFR and to be independent of IL‑6 and ‑22. Treatment with the STAT3 inhibitor NSC 74859 was able to reverse the TKI exposure‑induced chemoresistance in EGFR‑wt NSCLC cells. Similar phenomena were observed in H1975 cells harboring EGFR L858R and T790M mutations. Based on the observed molecular events following long exposure of an EGFR‑wt NSCLC cell line to an EGFR‑TKI, this study indicates that such drugs should be not recommended for EGFR‑wt patients who can undergo chemotherapy. This study also suggests that STAT3 inhibitors may aid in the treatment NSCLC patients who exhibit EGFR‑TKI resistance due to an acquired T790M mutation.
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View References

1 

Riely GJ, Politi KA, Miller VA and Pao W: Update on epidermal growth factor receptor mutations in non-small cell lung cancer. Clin Cancer Res. 12:7232–7241. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Ono M and Kuwano M: Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res. 12:7242–7251. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Mok TS, Wu YL, Thongprasert S, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Zhou C, Wu YL, Chen G, et al: Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 12:735–742. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Maemondo M, Inoue A, Kobayashi K, et al: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Laurie SA and Goss GD: Role of epidermal growth factor receptor inhibitors in epidermal growth factor receptor wild-type non-small-cell lung cancer. J Clin Oncol. 31:1061–1069. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Gatzemeier U, Pluzanska A, Szczesna A, et al: Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol ASCO. 22:abs. 7010. 2004.

8 

Han JY, Park K, Kim SW, et al: First-SIGNAL: first-line single-agent Iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 30:1122–1128. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Pirker R, Pereira JR, von Pawel J, et al: EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 13:33–42. 2012. View Article : Google Scholar

10 

Gridelli C, Ciardiello F, Gallo C, et al: First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 30:3002–3011. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Wu JY, Shih JY, Yang CH, et al: Second-line treatments after first-line gefitinib therapy in advanced nonsmall cell lung cancer. Int J Cancer. 126:247–255. 2010. View Article : Google Scholar

12 

Kumar A, Petri ET, Halmos B and Boggon TJ: Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J Clin Oncol. 26:1742–1751. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Kolch W and Pitt A: Functional proteomics to dissect tyrosine kinase signalling pathways in cancer. Nat Rev Cancer. 10:618–629. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Sebastian S, Settleman J, Reshkin SJ, Azzariti A, Bellizzi A and Paradiso A: The complexity of targeting EGFR signalling in cancer: from expression to turnover. Biochim Biophys Acta. 1766:120–139. 2006.PubMed/NCBI

15 

Normanno N, De Luca A, Bianco C, et al: Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 366:2–16. 2006. View Article : Google Scholar

16 

Irmer D, Funk JO and Blaukat A: EGFR kinase domain mutations - functional impact and relevance for lung cancer therapy. Oncogene. 26:5693–5701. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Kobayashi S, Boggon TJ, Dayaram T, et al: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 352:786–792. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Garassino MC, Martelli O, Broggini M, et al: Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 14:981–988. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Yang J, Cheng Y, Zhao M, Zhou K, Yan H and Zhang L: A phase II trial comparing pemetrexed with gefitinib as the second-line treatment of nonsquamous NSCLC patients with wild-type EGFR (CTONG0806). J Clin Oncol ASCO. 31:abs. 8042. 2013.

20 

Rosell R, Carcereny E, Gervais R, et al: Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13:239–246. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Mitsudomi T, Morita S, Yatabe Y, et al: Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 11:121–128. 2010. View Article : Google Scholar

22 

Kobayashi K, Inoue A, Maemondo M, et al: First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: a phase III study (002) by North East Japan Gefitinib Study Group. J Clin Oncol ASCO. 27:abs. 8016. 2009.

23 

Sequist LV, Bell DW, Lynch TJ and Haber DA: Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol. 25:587–595. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Maheswaran S, Sequist LV, Nagrath S, et al: Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 359:366–377. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Wu K, Chang Q, Lu Y, et al: Gefitinib resistance resulted from STAT3-mediated Akt activation in lung cancer cells. Oncotarget. 4:2430–2438. 2013.PubMed/NCBI

26 

Barré B, Vigneron A, Perkins N, Roninson IB, Gamelin E and Coqueret O: The STAT3 oncogene as a predictive marker of drug resistance. Trends Mol Med. 13:4–11. 2007. View Article : Google Scholar

27 

Dauer DJ, Ferraro B, Song L, et al: Stat3 regulates genes common to both wound healing and cancer. Oncogene. 24:3397–3408. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Ai T, Wang Z, Zhang M, et al: Expression and prognostic relevance of STAT3 and cyclin D1 in non-small cell lung cancer. Int J Biol Markers. 27:e132–e138. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Yamanaka Y, Nakajima K, Fukada T, Hibi M and Hirano T: Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation. EMBO J. 15:1557–1565. 1996.PubMed/NCBI

30 

Germain D and Frank DA: Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy. Clin Cancer Res. 13:5665–5669. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Dimberg A, Karlberg I, Nilsson K and Oberg F: Ser727/Tyr701- phosphorylated Stat1 is required for the regulation of c-Myc, cyclins, and p27Kip1 associated with ATRA-induced G0/G1 arrest of U-937 cells. Blood. 102:254–261. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Ramana CV, Chatterjee-Kishore M, Nguyen H and Stark GR: Complex roles of Stat1 in regulating gene expression. Oncogene. 19:2619–2627. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Dimco G, Knight RA, Latchman DS and Stephanou A: STAT1 interacts directly with cyclin D1/Cdk4 and mediates cell cycle arrest. Cell cycle. 9:4638–4649. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Yamashita S, Miyagi C, Fukada T, Kagara N, Che YS and Hirano T: Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature. 429:298–302. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Yadav A, Kumar B, Datta J, Teknos TN and Kumar P: IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 9:1658–1667. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Wang H, Zhang G, Zhang H, et al: Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell-like properties in cisplatin-resistant lung cancer cells through AKT/β-catenin/Snail signaling pathway. Eur J Pharmacol. 723:156–166. 2014. View Article : Google Scholar

37 

Lin L and Bivona TG: Mechanisms of resistance to epidermal growth factor receptor inhibitors and novel therapeutic strategies to overcome resistance in NSCLC patients. Chemother Res Pract. 2012:8172972012.PubMed/NCBI

38 

Chen Y-F and Fu L-W: Mechanisms of acquired resistance to tyrosine kinase inhibitors. Acta Pharm Sin B. 1:197–207. 2011. View Article : Google Scholar

39 

Yeh HH, Lai WW, Chen HH, Liu HS and Su WC: Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. Oncogene. 25:4300–4309. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Lee HJ, Zhuang G, Cao Y, Du P, Kim HJ and Settleman J: Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell. 26:207–221. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Kim SM, Kwon OJ, Hong YK, et al: Activation of IL-6R/JAK1/STAT3 signaling induces de novo resistance to irreversible EGFR inhibitors in non-small cell lung cancer with T790M resistance mutation. Mol Cancer Ther. 11:2254–2264. 2012. View Article : Google Scholar : PubMed/NCBI

42 

Song L, Rawal B, Nemeth JA and Haura EB: JAK1 activates STAT3 activity in non-small-cell lung cancer cells and IL-6 neutralizing antibodies can suppress JAK1-STAT3 signaling. Mol Cancer Ther. 10:481–494. 2011. View Article : Google Scholar : PubMed/NCBI

43 

Goldberg SB, Oxnard GR, Digumarthy S, et al: Chemotherapy with Erlotinib or chemotherapy alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors. Oncologist. 18:1214–1220. 2013. View Article : Google Scholar : PubMed/NCBI

44 

Haura EB, Sommers E, Song L, Chiappori A and Becker A: A pilot study of preoperative gefitinib for early-stage lung cancer to assess intratumor drug concentration and pathways mediating primary resistance. J Thorac Oncol. 5:1806–1814. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tang J, Guo F, Du Y, Liu X, Qin Q, Liu X, Yin T, Jiang L and Wang Y: Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3. Int J Oncol 46: 2083-2095, 2015.
APA
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X. ... Wang, Y. (2015). Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3. International Journal of Oncology, 46, 2083-2095. https://doi.org/10.3892/ijo.2015.2898
MLA
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X., Yin, T., Jiang, L., Wang, Y."Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3". International Journal of Oncology 46.5 (2015): 2083-2095.
Chicago
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X., Yin, T., Jiang, L., Wang, Y."Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3". International Journal of Oncology 46, no. 5 (2015): 2083-2095. https://doi.org/10.3892/ijo.2015.2898
Copy and paste a formatted citation
x
Spandidos Publications style
Tang J, Guo F, Du Y, Liu X, Qin Q, Liu X, Yin T, Jiang L and Wang Y: Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3. Int J Oncol 46: 2083-2095, 2015.
APA
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X. ... Wang, Y. (2015). Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3. International Journal of Oncology, 46, 2083-2095. https://doi.org/10.3892/ijo.2015.2898
MLA
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X., Yin, T., Jiang, L., Wang, Y."Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3". International Journal of Oncology 46.5 (2015): 2083-2095.
Chicago
Tang, J., Guo, F., Du, Y., Liu, X., Qin, Q., Liu, X., Yin, T., Jiang, L., Wang, Y."Continuous exposure of non‑small cell lung cancer cells with wild‑type EGFR to an inhibitor of EGFR tyrosine kinase induces chemoresistance by activating STAT3". International Journal of Oncology 46, no. 5 (2015): 2083-2095. https://doi.org/10.3892/ijo.2015.2898
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