Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment
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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.
KeywordsTumor volume Retinoblastoma Apoptosis Transplant Proliferation
- 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar