Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growth in vitro and in vivo
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Siao-Syun Guan1,2, Jungshan Chang3, Chun-Chia Cheng2,3, Tsai-Yueh Luo2, Ai-Sheng Ho4, Chia-Chi Wang5, Cheng-Tien Wu1 and Shing-Hwa Liu1,6,7
1 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
2 Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan
3 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
4 Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan
5 Division of Hepatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
6 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
7 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
Shing-Hwa Liu, email:
Keywords: colorectal cancer / HER2 / afatinib / micelles
Received: March 31, 2014 Accepted: May 30, 2014 Published: June 1, 2014
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.
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