Abstract
Trastuzumab has been recently approved for clinical use to treat HER2-expressing advanced gastric cancer, and anti-HER2-targeting therapy has become a promising option for gastric cancer. Lapatinib is a dual tyrosine kinase inhibitor targeting EGFR and HER2. The aim of the present study was to explore the utility of lapatinib for gastric cancer, with a particular focus on trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Nine gastric cancer cell lines were evaluated for the effects of lapatinib on the cell-surface accumulation of HER2 and analyzed for their additional effects on trastuzumab-mediated ADCC. Also, HER2 signaling with Western blot, proliferative function with the MTT assay, and apoptosis-inducing activity with 7ADD/Annexin-V were investigated when a panel of gastric cancer cell lines was treated with lapatinib. Lapatinib inhibited HER2 signaling and cell proliferation in the panel of gastric cancer cell lines. Lapatinib also induced the accumulation of HER2 on the cell surface, resulting in the enhancement of trastuzumab-mediated ADCC of gastric cancer. Lapatinib exhibits inhibitory activity in gastric cancer cells, and the combination of lapatinib with trastuzumab may be a promising treatment strategy for gastric cancer patients.
Highlights
About 110,000 people in Japan develop gastric cancer and an estimated 65,000 die from it, which is second among cancer-related deaths in the country [1]
Background Trastuzumab has been recently approved for clinical use to treat HER2-expressing advanced gastric cancer, and anti-HER2-targeting therapy has become a promising option for gastric cancer
A panel of gastric cancer cell lines were tested for HER2 expression on the cell surface by flow cytometry following exposure to Dimethyl sulfoxide (DMSO) as control or several doses of lapatinib for 48 h (Fig. 1)
Summary
About 110,000 people in Japan develop gastric cancer and an estimated 65,000 die from it, which is second among cancer-related deaths in the country [1]. Despite multimodality therapy such as surgical resection combined with chemotherapy, hyperthermia, and chemoradiotherapy, the prognosis with advanced disease remains poor [2,3,4,5,6,7]. HER2 signaling with Western blot, proliferative function with the MTT assay, and apoptosis-inducing activity with 7ADD/Annexin-V were investigated when a panel of gastric cancer cell lines was treated with lapatinib.
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