title: Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growth in vitro and in vivo.
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.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
authors.forename: Siao-Syun
authors.initials: SS
authors.lastname: Guan
authors.forename: Jungshan
authors.initials: J
authors.lastname: Chang
authors.forename: Chun-Chia
authors.initials: CC
authors.lastname: Cheng
authors.forename: Tsai-Yueh
authors.initials: TY
authors.lastname: Luo
authors.forename: Ai-Sheng
authors.initials: AS
authors.lastname: Ho
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.forename: Cheng-Tien
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004339:Drug Compounding; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D061986:MCF-7 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D008875:Middle Aged; D011108:Polymers / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000077716:Afatinib; D008823:Micelles; D011108:Polymers; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases