Abstract: Objective To explore the feasibility of HER2-negative gastric cancer cell lines benefiting from trastuzumab treatment after exogenous HER2 gene introduction. Methods Human HER2 eukaryotic expression vector was constructed and transfected to human gastric cancer cell lines (HGC-27 and MGC803) and normal gastric epithelial cell GES1 (as control). Immunofluorescence and Western blot were employed to detect HER2 and its downstream signaling pathways, and CCK-8 assay was used to measure the viability of cells. Results After the introduction of exogenous HER2 into HER2- negative gastric cancer cells and normal cells, HER2 was significantly upregulated rather than phosphorylated HER2 (pHER2). Also, the sensitivity of HER2-negative cells to trastuzumab wasn’t increased after the introduction of exogenous HER2. In addition, PI3K/AKT and MAPK pathways were not activated but significantly inhibited after the introduction of exogenous HER2. Conclusions Exogenous HER2 introduction cannot benefit HER2-negative gastric cancer from trastuzumab treatment. The main reason might be that exogenous HER2 does not activate its downstream PI3K/AKT and MAPK pathways. The role of exogenous and endogenous HER2 may be different, which will be explored in further study.

Key words: exogenous HER2, HER2-negative gastric cancer, trastuzumab