Tetraiodothyroacetic acid and its nanoformulation inhibit thyroid hormone stimulation of non-small cell lung cancer cells in vitro and its growth in xenografts
LUNG CANCER, cilt.76, sa.1, ss.39-45, 2012 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 76 Sayı: 1
- Basım Tarihi: 2012
- Doi Numarası: 10.1016/j.lungcan.2011.10.003
- Dergi Adı: LUNG CANCER
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.39-45
- Anahtar Kelimeler: Non-small cell lung cancer, Thyroid hormone, Tetrac, Tetrac nanoparticles, Angiogenesis, Cell surface integrin alpha v beta 3 receptor, Cancer, ACTIVATED PROTEIN-KINASE, SURFACE RECEPTOR, L-THYROXINE, INTEGRIN, HYPOTHYROIDISM, CARCINOMA, TETRAC, GLIOMA, 3,5,3'-TRIIODO-L-THYRONINE, PROLIFERATION
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
Thyroid hormone stimulates cell proliferation of several types of cancers and stimulates cancer-relevant angiogenesis. In the present study, we investigated the proliferative effect of thyroid hormone and the anti-proliferative and anti-angiogenic action of its nano-derivative, tetrac-NP, on human non-small cell lung cancer (NSCLC) H1299 cells in vitro and in xenografts. The anti-proliferative activity of unmodified tetrac and tetrac-NP against human H1299 cells was determined in three models: (a) cultured H1299 cells in vitro, (b) tumor cell implants in the fertilized chick chorioallantoic membrane (CAM) system and (c) xenografts in the nude mouse. An integrin alpha v beta 3 antibody inhibited thyroid hormone-induced cell proliferation in vitro, as did unmodified tetrac and tetrac-NP. Pharmacologic inhibition of the mitogen-activated protein kinase pathway also blocked NSCLC cell proliferation in response to thyroid hormone. Tetrac and tetrac-NP arrested tumor growth and tumor-related angiogenesis in H1299 cells grown in the CAM model and both agents prevented chick embryo mortality. Xenografts of H1299 cells were established in nude mice (n = 8, treatment and control groups) and when tumor volumes reached 250-300 mm(3), tetrac (1 mg/kg) or tetrac-NP (1 mg tetrac as the nanoparticle/kg) were administered intraperitoneally every 2 days. Tetrac and tetrac-NP significantly suppressed tumor growth and angiogenesis. Thus, both tetrac and tetrac-NP effectively arrest human NSCLC tumor cell proliferation in vitro and in the CAM assay and in murine xenograft models. (C) 2011 Elsevier Ireland Ltd. All rights reserved.