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In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations

  • Authors:
    • Shu‑Zhi Zang
    • Yan‑Rong Yang
    • Sha‑Sha Zhao
    • Yun‑Xia Li
    • Xin‑Yuan Gao
    • Chun‑Lei Zhong
  • View Affiliations / Copyright

    Affiliations: Department of Respiration, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
    Copyright: © Zang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1735-1740
    |
    Published online on: March 2, 2017
       https://doi.org/10.3892/etm.2017.4168
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Abstract

The T790M mutational basis of treatment failure, following treatment via alteration of the epidermal growth factor receptor (EGFR) pathway, is a well‑known anomaly in patients with non‑small cell lung cancer (NSCLC). The T790M mutation activates the kinase domain, causing tyrosine kinase inhibitors, such as gefitinib, to elicit little or no response. To overcome this acquired resistance in NSCLC cells, the present study utilized a structure‑based drug designing method to identify a novel lead compound. An in‑house traditional Chinese medicinal compound database was used and following initial virtual screening, pre‑absorption, distribution, metabolism and excretion/Tox and automated docking analyses, nardosinon was selected as the most appropriate candidate for further analysis. Two NSCLC cell lines, PC9GR4 and H2347, were used to test nardosinon and the results were compared with gefitinib. Results from an initial cell death assay revealed that nardosinon was able to induce cell death in NSCLC cells with and without the T790M mutation. These findings suggest that nardosinon may be an effective pharmacological compound for NSCLC treatment, including T790M EGFR mutant NSCLC cells.
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1 

Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG and Halmos B: 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

2 

Wang J, Jiang Y, Liang H, Li P, Xiao H, Ji J, Xiang W, Shi JF, Fan YG, Li L, et al: Attributable causes of cancer in China. Ann Oncol. 23:2983–2999. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, et al: Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 20:4285–4291. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Mendelsohn J and Baselga J: Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol. 21:2787–2799. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J, Krug LM, Pao W, Rizvi N, Pizzo B, et al: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 22:1103–1109. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, et al: Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomised phase 3 trial. Lancet Oncol. 15:213–222. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Gervas P, Ivanova A, Vasiliev N, Ananina O, Zharkova O, Rogovieva O, Verzhbitskaya N, Didichuk I, Cheremisina O, Popova N, et al: Frequency of EGFR mutations in non-small cell lung cancer patients: Screening data from west siberia. Asian Pac J Cancer Prev. 16:689–792. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Chao TT, Wang CY, Lai CC, Chen YL, Tsai YT, Chen PT, Lin HI, Huang YC, Shiau CW, Yu CJ and Chen KF: TD-19, an erlotinib derivative, induces epidermal growth factor receptor wild-type nonsmall-cell lung cancer apoptosis through CIP2A-mediated pathway. J Pharmacol Exp Ther. 351:352–358. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Linardou H, Dahabreh IJ, Bafaloukos D, Kosmidis P and Murray S: Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol. 6:352–366. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Helena AY, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M and Riely GJ: Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 19:2240–2247. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Gandhi J, Zhang J, Xie Y, Soh J, Shigematsu H, Zhang W, Yamamoto H, Peyton M, Girard L, Lockwood WW, et al: Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines. PLoS One. 4:e45762009. View Article : Google Scholar : PubMed/NCBI

12 

Fan XX, Wong MP, Cao ZW, Li N, Wu JL, Zhou H, Jiang Z, Liu L and Leung E: Abstract 3193: Apoptotic effect of a single compound derived from natural product in Gefitinib-resistant non-small cell lung cancer cells. Cancer Res. 74:2014. View Article : Google Scholar

13 

Chikan NA, Bhavaniprasad V, Anbarasu K, Shabir N and Patel TN: From natural products to drugs for epimutation computer-aided drug design. Appl Biochem Biotechnol. 170:164–175. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C, Horne E, Lackey K, et al: A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib) Relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 64:6652–6659. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Guex N and Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis. 18:2714–2723. 1997. View Article : Google Scholar : PubMed/NCBI

16 

Trott O and Olson AJ: AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 31:455–461. 2010.PubMed/NCBI

17 

Seeliger D and de Groot BL: Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 24:417–422. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS and Olson AJ: AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 30:2785–2791. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Lipinski CA, Lombardo F, Dominy BW and Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 46:3–26. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M and Eck MJ: The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA. 105:2070–2075. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Bae GS, Kim MS, Park KC, Koo BS, Jo IJ, Choi SB, Lee DS, Kim YC, Kim TH, Seo SW, et al: Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis. World J Gastroenterol. 18:3223–3234. 2012.PubMed/NCBI

22 

Li W, Shi J, Li Q, Duan HH and Tang MK: Nardosinone reduces neuronal injury induced by oxygen-glucose deprivation in primary cortical cultures. Yao Xue Xue Bao. 48:1422–1429. 2013.(In Chinese). PubMed/NCBI

23 

Ju SM, Lee J, Kang JG, Jeong SO, Park JH, Pae HO, Lee GS, Kim WS, Lyu YS and Jeon BH: Nardostachys chinensis induces granulocytic differentiation with the suppression of cell growth through p27(Kip1) protein-related G0/G1 phase arrest in human promyelocytic leukemic cells. Pharm Biol. 53:1002–1009. 2015. View Article : Google Scholar : PubMed/NCBI

24 

More SV, Koppula S, Kim IS, Kumar H, Kim BW and Choi DK: The role of bioactive compounds on the promotion of neurite outgrowth. Molecules. 17:6728–6753. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Ahmad A, Sattar MZ, Rathore HA, Fatima T, Khan SA, Afzal S, Lazhari M, Ahmed FU and Eseyin O: Pharmacological importance of Nardostachys jatamansi DC: A potential therapeutic agent in different pathological ailments. J Chem Pharmaceutical Res. 5:431–438. 2013.

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Copy and paste a formatted citation
Spandidos Publications style
Zang SZ, Yang YR, Zhao SS, Li YX, Gao XY and Zhong CL: In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations. Exp Ther Med 13: 1735-1740, 2017.
APA
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., & Zhong, C. (2017). In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations. Experimental and Therapeutic Medicine, 13, 1735-1740. https://doi.org/10.3892/etm.2017.4168
MLA
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., Zhong, C."In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations". Experimental and Therapeutic Medicine 13.5 (2017): 1735-1740.
Chicago
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., Zhong, C."In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations". Experimental and Therapeutic Medicine 13, no. 5 (2017): 1735-1740. https://doi.org/10.3892/etm.2017.4168
Copy and paste a formatted citation
x
Spandidos Publications style
Zang SZ, Yang YR, Zhao SS, Li YX, Gao XY and Zhong CL: In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations. Exp Ther Med 13: 1735-1740, 2017.
APA
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., & Zhong, C. (2017). In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations. Experimental and Therapeutic Medicine, 13, 1735-1740. https://doi.org/10.3892/etm.2017.4168
MLA
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., Zhong, C."In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations". Experimental and Therapeutic Medicine 13.5 (2017): 1735-1740.
Chicago
Zang, S., Yang, Y., Zhao, S., Li, Y., Gao, X., Zhong, C."In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations". Experimental and Therapeutic Medicine 13, no. 5 (2017): 1735-1740. https://doi.org/10.3892/etm.2017.4168
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