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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 355 - 364 (10page)
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Purpose HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in colorectal cancer (CRC) cell lines.
Materials and Methods The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between two drugs was evaluated by the com- bination index.
Results The addition of HM781-36B induced potent growth inhibition in both DiFi cells with epider- mal growth factor receptor (EGFR) overexpression and SNU-175 cells (IC50, 0.003 µM and 0.005 µM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells.
Conclusion These findings suggest the potential roles of HM781-36B as the treatment for EGFR-over- expressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.
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참고문헌 (25)
참고문헌 신청
Venook A / 2005 / Critical evaluation of current treatments in metastatic colorectal cancer / Oncologist 10:250~261
McKay JA / 2002 / Evaluation of the epidermal growth factor receptor(EGFR)in colorectal tumours and lymph node metastases / Eur J Cancer 38:2258~2264
Hynes NE / 2005 / ERBB receptors and cancer : the complexity of targeted inhibitors / Nat Rev Cancer 5:341~354
Wong SF / 2005 / Cetuximab : an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer / Clin Ther 27:684~694
Kobayashi S / 2005 / EGFR mutation and resistance of nonsmall-cell lung cancer to gefitinib / N Engl J Med 352:786~792
McKay JA / 2002 / Evaluation of the epidermal growth factor receptor(EGFR)in colorectal tumours and lymph node metastases / Eur J Cancer 38:2258~2264
Hynes NE / 2005 / ERBB receptors and cancer : the complexity of targeted inhibitors / Nat Rev Cancer 5:341~354
Wong SF / 2005 / Cetuximab : an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer / Clin Ther 27:684~694
Kobayashi S / 2005 / EGFR mutation and resistance of nonsmall-cell lung cancer to gefitinib / N Engl J Med 352:786~792
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