S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Antitumor activity of HM781-36B, a pan-HER tyrosine kinase inhibitor, in HER2-amplified breast cancer cells
- Kim, Hye Jin; Kim, Hwang-Phill; Yoon, Young-Kwang; Kim, Maeng-Sup; Lee, Gwan-Sun; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue
- Issue Date
- Anti-Cancer Drugs, Vol.23 No.3, pp.288-297
- HM781-36B is an orally administered pan-human epidermal growth factor receptor (HER) inhibitor. To explore the role of pan-HER inhibitor in breast cancer, we investigated the antitumor effect and mechanisms of HM781-36B in breast cancer cell lines. Six breast cancer cell lines (BT474, MDA-MB-453, SK-BR-3, T47D, MCF-7, and MDA-MB-231) were tested. The growth inhibitory effect was assessed using the tetrazolium bromide [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide] assay. The cell cycle at various concentrations of HM781-36B was analyzed by flow cytometry, and analysis of downstream molecules was performed by western blot analysis. Interaction of HM781-36B with cytotoxic chemotherapeutic agents was analyzed by combination index using CalcuSyn. The HER2-amplified cells (SK-BR-3, BT474, and MDA-MB-453) were sensitive to HM781-36B (IC50 = 0.001 mu mol/l, 0.0012 mu mol/l, and 0.0095 mu mol/l, respectively). HM781-36B induced G1 arrest and resulted in apoptosis. It reduced the level of p-HER2, p-AKT, p-ERK, and p-STAT3. HM781-36B combined with 5-fluorouracil, cisplatin, paclitaxel, or gemcitabine showed a synergistic inhibitory effect on the HER2-amplified and on some of the HER2-nonamplified breast cancer cells. HM781-36B could be a promising treatment for HER2-amplified breast cancer as a single agent or in combination with cytotoxic agents and can be a candidate for treatment of HER2-nonamplified breast cancer in combination with cytotoxic agents. Anti-Cancer Drugs 23: 288-297 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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