Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in Colorectal Cancer Cells.
- Author:
Mi Hyun KANG
1
;
Sung Ung MOON
;
Ji Hea SUNG
;
Jin Won KIM
;
Keun Wook LEE
;
Hye Seung LEE
;
Jong Seok LEE
;
Jee Hyun KIM
Author Information
- Publication Type:Original Article
- Keywords: HM781-36B; Colorectal neoplasm; Epidermal growth factor receptor-neu receptor; BMX
- MeSH: Apoptosis; Cell Cycle; Cell Line; Cell Survival; Colonic Neoplasms; Colorectal Neoplasms*; Cytoplasm; Flow Cytometry; Fluorouracil; Humans; Phosphotransferases; Protein-Tyrosine Kinases; Receptor, Epidermal Growth Factor
- From:Cancer Research and Treatment 2016;48(1):355-364
- CountryRepublic of Korea
- Language:English
- 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 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 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.
