Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growth in vitro and in vivo

Siao Syun Guan, Jungshan Chang, Chun Chia Cheng, Tsai Yueh Luo, Ai Sheng Ho, Chia Chi Wang, Cheng Tien Wu, Shing Hwa Liu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is known as a common malignant neoplasm worldwide. The role of EGFR/HER2 in CRC is unclear. Afatinib is an irreversible EGFR/HER2 inhibitor. There were few studies of afatinib on CRC. Here, we investigated the protein levels/expressions of HER2 in sera and tumors from CRC patients and the therapeutic effect of afatinib on HER2-overexpressed CRC in vitro and in vivo. The increased HER2 levels were detected in the collected sera and tumors of patients with CRC. The serological HER2 levels were correlated with the tumor HER2 expressions in patients. Afatinib also inhibited the HER2-positive tumor cell growth and caused apoptosis in HER2-overexpressed human colorectal cancer HCT-15 cells but not in low HER2 expressed human gastric cancer MKN45 cells. In vivo study showed that afatinib reduced tumor growth in HER2-overexpressed xenografts. Moreover, afatinib-encapsulated micelles displayed higher cytotoxic activity in HCT-15 cells and were more effective for tumor growth suppression in HCT-15-induced tumor xenografts than afatinib performance alone. Taken together, these findings suggest that higher serum HER2 levels reflect the higher HER2 contents in tumors of CRC patients, and the improved afatinib-encapsulated micelles possess high therapeutic efficacy in HER2-overexpressed CRC in vitro and in vivo.

Original languageEnglish
Pages (from-to)4868-4880
Number of pages13
JournalOncotarget
Volume5
Issue number13
Publication statusPublished - 2014

Keywords

  • Afatinib
  • Colorectal cancer
  • HER2
  • Micelles

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growth in vitro and in vivo'. Together they form a unique fingerprint.

  • Cite this

    Guan, S. S., Chang, J., Cheng, C. C., Luo, T. Y., Ho, A. S., Wang, C. C., Wu, C. T., & Liu, S. H. (2014). Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growth in vitro and in vivo. Oncotarget, 5(13), 4868-4880.