DOI QR코드

DOI QR Code

ZD1839 and Cisplatin Alone or in Combination for Treatment of a Nasopharyngeal Carcinoma Cell Line and Xenografts

  • Gu, Wei-Guang (Department of Medical Oncology, Nanhai District People's Hospital) ;
  • Huang, Yan (Department of Medical Oncology, Sun Yat-Sen University Cancer Center) ;
  • Yuan, Zhong-Yu (Department of Medical Oncology, Sun Yat-Sen University Cancer Center) ;
  • Peng, Rou-Jun (Department of Medical Oncology, Sun Yat-Sen University Cancer Center) ;
  • Luo, Hai-Tao (Department of Medical Oncology, Nanhai District People's Hospital) ;
  • He, Zhi-Ren (Department of Medical Oncology, Nanhai District People's Hospital) ;
  • Wang, Shu-Sen (Department of Medical Oncology, Sun Yat-Sen University Cancer Center)
  • Published : 2013.03.30

Abstract

This study evaluated the effects of ZD1839, an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Influence of ZD1839 alone or combined with cisplatin on the NPC cell line CNE2 was detected by MTT assay with flow cytometry assessment of cell cycle distribution and apoptosis rates. Nude mice NPC xenografts were also used to evaluate the effects of ZD1839 alone or combined with cisplatin. The Student's t test evaluated statistical significance. ZD1839 alone or combined with cisplatin inhibited CNE2 cell line proliferation. ZD1839 induced CNE2 cell cycle arrest in the G1 phase, and higher concentrations induced apoptosis. Xenograft tumors were significantly smaller when treated with 200 mg/kg ZD1839, cisplatin, or cisplatin combined with 100 mg/kg ZD1839 than untreated controls. ZD1839 (200 mg/kg) alone showed good tumor inhibition effects, reduction of tumor weights, and smaller tumor volume without loss of body weight. ZD1839 (200 mg/kg) might provide a good and effective therapeutic reagent for NPC.

References

  1. Adelstein DJ, Rodriguez CP, Rybicki LA, et al (2012). A phase II trial of gefitinib for recurrent or metastatic cancer of the esophagus or gastroesophageal junction. Invest New Drugs, 30, 1684-9. https://doi.org/10.1007/s10637-011-9736-z
  2. Barker AJ, Gibson KH, Grundy W, et al (2001). Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett, 11, 1911-4. https://doi.org/10.1016/S0960-894X(01)00344-4
  3. Chan SL, Ma BB (2012). Novel systemic therapeutic for nasopharyngeal carcinoma. Expert Opin Ther Targets, 16, S63-8. https://doi.org/10.1517/14728222.2011.635646
  4. Chua DT, Wei WI, Wong MP, et al (2008). Phase II study of gefitinib for the treatment of recurrent and metastatic nasopharyngeal carcinoma. Head Neck, 30, 863-7. https://doi.org/10.1002/hed.20792
  5. Ciardiello F, Caputo R, Bianco R, et al (2000). Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res, 6, 2053-63.
  6. Ciardiello F, Caputo R, Bianco R, et al (2001). Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res, 7, 1459-65.
  7. Ciardiello F, Tortora G (2001). A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res, 7, 2958-70.
  8. Cohen MH, Williams GA, Sridhara R, et al (2003). FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist, 8, 303-6. https://doi.org/10.1634/theoncologist.8-4-303
  9. Engebraaten O, Edvardsen H, Løkkevik E, et al (2012). Gefitinib in combination with weekly docetaxel in patients with metastatic breast cancer caused unexpected toxicity: results from a randomized phase II clinical trial. ISRN Oncol, 2012, 176789.
  10. Gejyo F, Chang JL, Burgi W, et al (1983) Characterization of the B-chain of human plasma alpha 2HS-glycoprotein. The complete amino acid sequence and primary structure of its heteroglycan. J Biol Chem, 258, 4966-71.
  11. Gregoire V, Hamoir M, Chen C, et al (2011). Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study. Radiother Oncol, 100, 62-9. https://doi.org/10.1016/j.radonc.2011.07.008
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  13. Joensuu G, Joensuu T, Nupponen N, et al (2012). A phase II trial of gefitinib in patients with rising PSA following radical prostatectomy or radiotherapy. Acta Oncol, 51, 130-3. https://doi.org/10.3109/0284186X.2011.617387
  14. Kindler HL, Friberg G, Skoog L, et al (2005). Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer. Am J Clin Oncol, 28, 340-4. https://doi.org/10.1097/01.coc.0000159558.19631.d5
  15. Lee AW, Lin JC, Ng WT (2012). Current management of nasopharyngeal cancer. Semin Radiat Oncol, 22, 233-44. https://doi.org/10.1016/j.semradonc.2012.03.008
  16. Lewis CM, Glisson BS, Feng L, et al (2012). A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck. Clin Cancer Res, 18, 1435-46. https://doi.org/10.1158/1078-0432.CCR-11-1951
  17. Ma BB, Kam MK, Leung SF, et al (2012). A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Ann Oncol, 23, 1287-92. https://doi.org/10.1093/annonc/mdr401
  18. Ranson M (2002). ZD1839 (Iressa): for more than just non-small cell lung cancer. Oncologist, 7, 16-24.
  19. Sirotnak FM (2003). Studies with ZD1839 in preclinical models. Semin Oncol, 30, 12-20.
  20. Wakeling AE, Guy SP, Woodburn JR, et al (2002). ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res, 62, 5749-54.
  21. Woodburn J, Kendrew J, Fennell M, et al (2000). ZD1839 ('Iressa') a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI): inhibition of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition. Proc Am Assoc Cancer Res, 41, 402.
  22. You B, Le Tourneau C, Chen EX, et al (2012). A Phase II trial of erlotinib as maintenance treatment after gemcitabine plus platinum-based chemotherapy in patients with recurrent and/or metastatic nasopharyngeal carcinoma. Am J Clin Oncol, 35, 255-60. https://doi.org/10.1097/COC.0b013e31820dbdcc

Cited by

  1. Mangiferin Induces Apoptosis by Regulating Bcl-2 and Bax Expression in the CNE2 Nasopharyngeal Carcinoma Cell Line vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7065
  2. microRNA Expression and Biogenesis in Cellular Response to Ionizing Radiation vol.33, pp.10, 2014, https://doi.org/10.1089/dna.2014.2401