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Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment

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Tumor Biology

Abstract

The present study investigates the effect of afatinib on the growth, induction of apoptosis in RB116 cells, and reduction of carcinoma growth in the mice transplanted with RB116 cells. The results from MTT assay revealed that afatinib inhibited the growth of RB116 cells in a dose-dependent manner. Proliferation of RB116 cells was reduced to 64 % on treatment with 200 μM concentration of afatinib after 48 h. Afatinib treatment of RB116 cells at 200 μM concentration induced apoptosis and necrosis in 49.7 and 9.4 %, respectively, after 48 h. In the RB116-transplanted mice, treatment with afatinib at 10-mg/kg doses for 45 days caused a significant (p < 0.005) reduction in the tumor volume compared to the control group. The tissue lysates of the mice containing RB116 transplant showed a significant decrease in the expressions of Ki67 and p53 in the afatinib treatment group after 45 days. However, the expression of caspase-3 was increased and of Bcl-2 remained unaltered on treatment with afatinib. Measurement of the body weight of afatinib-treated animals showed no reduction during the study. Thus, afatinib can be of therapeutic value for the treatment of retinoblastoma.

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References

  1. Albert DM. Historic review of retinoblastoma. Ophthalmology. 1987;94:654–62.

    Article  CAS  PubMed  Google Scholar 

  2. Shields JA, Shields CL. Current management of retinoblastoma. Mayo Clin Proc. 1994;69:50–6.

    Article  CAS  PubMed  Google Scholar 

  3. Bishop JO, Madsen EC. Retinoblastoma; review of the current status. Surv Ophthalmol. 1975;19:342–66.

    CAS  PubMed  Google Scholar 

  4. Yanagisawa T. Systemic chemotherapy as a new conservative treatment for intraocular retinoblastoma. Int J Clin Oncol. 2004;9:13–24.

    Article  CAS  PubMed  Google Scholar 

  5. Rodriguez-Galindo C, Wilson MW, Haik BG, Merchant TE, Billups CA, Shaha N, et al. Treatment of intraocular retinoblastoma with vincristine and carboplatin. J Clin Oncol. 2003;21:2019–25.

    Article  CAS  PubMed  Google Scholar 

  6. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16:15–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang H, Berezov A, Wang Q, et al. ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest. 2007;117:2051–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.

    Article  CAS  PubMed  Google Scholar 

  9. Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27:4702–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Harbeck N, Solca F, Gauler TC. Preclinical and clinical development of afatinib: a focus on breast cancer and squamous cell carcinoma of the head and neck. Future Oncol. 2014;10:21–40.

    Article  CAS  PubMed  Google Scholar 

  11. Tsai YC, Yeh CH, Tzen KY, Ho PY, Tuan TF, Pu YS, et al. Targeting epidermal growth factor receptor/human epidermal growth factor receptor 2 signalling pathway by a dual receptor tyrosine kinase inhibitor afatinib for radiosensitisation in murine bladder carcinoma. Eur J Cancer. 2013;49:1458–66.

    Article  CAS  PubMed  Google Scholar 

  12. Quesnelle KM, Grandis JR. Dual kinase inhibition of EGFR and HER2 overcomes resistance to cetuximab in a novel in vivo model of acquired cetuximab resistance. Clinical Cancer Research. 2011;17:5935–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Greulich H, Kaplan B, Mertins P, Chen TH, Tanaka KE, Yun CH, et al. Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ErbB2. Proc Natl Acad Sci USA. 2012;109:14476–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cardillo MR, Castagna G, Memeo L, De Bernardinis E, Di Silverio F. Epidermal growth factor receptor, MUC-1 and MUC-2 in bladder cancer. J Exp Clin Cancer Res. 2000;19:225–33.

    CAS  PubMed  Google Scholar 

  15. Caner V, Turk NS, Duzcan F, et al. No strong association between HER-2/neu protein overexpression and gene amplification in high-grade invasive urothelial carcinomas. Pathol Oncol Res. 2008;14:261–6.

    Article  PubMed  Google Scholar 

  16. Kiyoshima K, Oda Y, Kinukawa N, Naito S, Tsuneyoshi M. Overexpression of laminin-5 gamma2 chain and its prognostic significance in urothelial carcinoma of urinary bladder: association with expression of cyclooxygenase 2, epidermal growth factor receptor [corrected] and human epidermal growth factor receptor [corrected] 2. Hum Pathol. 2005;36:522–30.

    Article  CAS  PubMed  Google Scholar 

  17. Mori H, Honda K, Ishida R, Nohira T, Tomoda A. Antitumor activity of 2-amino-4,4α-dihydro-4α,7-dimethyl-3H- phenoxazine-3-one against Meth A tumor transplanted into BALB/c mice. Anticancer Drugs. 2000;11:653–7.

    Article  CAS  PubMed  Google Scholar 

  18. Shimamoto T, Tomoda A, Ishida R, Ohyashiki K. Antitumor effect of a novel derivative on human leukemia cell lines in vivo and in vitro. Clin Cancer Res. 2001;7:704–8.

    CAS  PubMed  Google Scholar 

  19. Koshibu-Koizumi J, Akazawa M, Iwamoto T, Takasaki M, Mizuno F, Kobayashi R, et al. Antitumor activity of a phenoxazine compound, 2-amino-4,4α-dihydro- 4α,7-dimethyl-3H-phenoxazine-3-one against human B cell and T cell lymphoblastoid cell lines: induction of mixed types of cell death apoptosis and necrosis. J Cancer Res Clin Oncol. 2002;128:363–8.

    Article  CAS  PubMed  Google Scholar 

  20. Healy E, Angus B, Lawrence CM, Rees JL. Prognostic value of Ki67 antigen expression in basal cell carcinomas. Br J Dermatol. 1995;133:737–41.

    Article  CAS  PubMed  Google Scholar 

  21. Lustosa SA, Logullo A, Artigiani R, Saad SS, Goldenberg A, Matos D. Analysis of the correlation between p53 and Bcl-2 expression with staging and prognosis of the colorectal adenocarcinoma. Acta Cir Bras. 2005;20:353–7.

    Article  PubMed  Google Scholar 

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Correspondence to Long-mei Wang.

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Zhan, Wj., Zhu, Jf. & Wang, Lm. Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment. Tumor Biol. 37, 9249–9254 (2016). https://doi.org/10.1007/s13277-015-4768-1

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  • DOI: https://doi.org/10.1007/s13277-015-4768-1

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