Inhibitory effects of combinations of trastuzumab and cytotoxic chemotherapy drugs in HER2-positive gastric cancer

Abstract

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a certain proportion of gastric cancer cases. Trastuzumab is a humanized monoclonal antibody that targets the HER2 receptor. Previous studies have demonstrated a synergistic interaction between trastuzumab and 5-fluorouracil/cisplatin in HER2-positive gastric cancer cells. However, it is unclear whether it is rational to combine trastuzumab with other chemotherapy regimens in clinical practice. We evaluated the growth inhibitory effects of combinations of trastuzumab and cytotoxic chemotherapy drugs in HER2-positive gastric cancer cell lines. HER2 protein expression was evaluated by Western blotting in five gastric cancer cell lines. MTT assays were performed to evaluate the growth inhibitory effects of trastuzumab and four chemotherapeutic agents, epirubicin, cisplatin, 5-fluorouracil and docetaxel, both alone and in combination. To explore the molecular mechanisms underlying the synergistic interactions of trastuzumab and chemotherapeutic agent treatment, the protein levels of phospho-protein kinase B (pAkt) were determined by Western blotting. We showed that trastuzumab synergizes with the cytotoxic effect of epirubicin in HER2-positive gastric cancer cells. Further investigation showed that the trastuzumab-epirubicin combination decreased the expression of pAkt. Altogether, our results provide preclinical evidence for the optimization of this combination regimen in the treatment of HER2-positive gastric cancer patients.