Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in Colorectal Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 355-364, 2016.
Article
in English
| WPRIM
| ID: wpr-64170
ABSTRACT
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 ANDMETHODS:
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 2 drugs was evaluated by the combination index.RESULTS:
The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 microM, 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-overexpressing 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphotransferases
/
Protein-Tyrosine Kinases
/
Colorectal Neoplasms
/
Cell Cycle
/
Cell Line
/
Cell Survival
/
Apoptosis
/
Colonic Neoplasms
/
Cytoplasm
/
ErbB Receptors
Limits:
Humans
Language:
English
Journal:
Cancer Research and Treatment
Year:
2016
Type:
Article
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