Guo-Hui Fu
Shanghai Jiao Tong University, China
Title: Combination of trastuzumab and gastrin inhibited growth of HER2-negative gastric cancer
Biography
Biography: Guo-Hui Fu
Abstract
Epidermal Growth Factor receptor 2 (HER2) is expressed in 6%-23% gastric cancer tissues. Administration of Trastuzumab, a fully humanized monoclonal antibody targeted to the HER2, is associated with survival rate in HER2-positive gastric cancer (GC) patients. Gastrin is a major gastrointestinal hormone proven to have an inhibitory eff ect on GC in vitro and in vivo. Here, we report the synergistic inhibitory eff ects of Trastuzumab and Gastrin on HER2-negative GC cells through the Gastrin/Cholecystokinin B receptor (CCKBR) pathway. Trastuzumab upregulated CCKBR protein levels but could not initiate its signal transduction, whereas Gastrin increased the levels and activation of CCKBR. Molecular experiments indicated that Trastuzumab and Gastrin co-treatment synergistically enhanced the stability of CCKBR. Moreover, their combined treatment synergistically arrested GC cells at G0/G1 phase, down-regulated levels of GC-related proteins, including anion exchanger (AE) 1, Cyclin D1, β-catenin and Cytoplasmic p16, and promoted nuclear translocation of p16. In addition, combination treatment upregulated AE2 levels, which are reduced in GC tissues. Th e in vivo synergistic anti-GC eff ect of combined treatment was confi rmed in xenograft experiments. Th e results demonstrated the synergistic eff ect of Gastrin and Trastuzumab in the suppression of GC