Abstract
Background Lapatinib is a small-molecule tyrosine kinase inhibitor that plays important roles in cell proliferation and survival. Administration of lapatinib with capecitabine is an effective treatment for HER2-positive metastatic BC. However, the effects of lapatinib on gastric cancer (GC) remain to be clear. In this study, we aimed to investigate the therapeutic effects of lapatinib combined with sulforaphane on GC and its underlying mechanisms. Methods SGC-7901 and lapatinib-resistant SGC-7901 cells were treated with lapatinib (0.2 μM), sulforaphane (5 μM), or their combinations. Cell viability, invasion, cycle, and apoptosis of SGC-7901 and lapatinib-resistant SGC-7901 cells were evaluated by thiazolyl blue tetrazolium bromide (MTT), Boyden chamber assay, and flow cytometer. The protein expressions of HER-2, p-HER-2, AKT, p-AKT, ERK, and p-ERK were detected by Western blotting. Results We observed that lapatinib combined with sulforaphane significantly decreased cell viability and inhibited cell migration of drug-sensitive and drug-resistant cells. Lapatinib sulforaphane also remarkably induced cell apoptosis with G0/G1 arrest. In addition, Western blotting revealed that the expressions of HER-2, p-HER-2, AKT, p-AKT, ERK, and p-ERK were downregulated by lapatinib-sulforaphane treatment. Conclusion Combination of lapatinib and sulforaphane might be a novel and promising therapeutic treatment for lapatinib-sensitive or lapatinib-resistant GC patients.
Highlights
Gastric cancer (GC) is one of the most common malignant tumors worldwide, with high morbidity and mortality [1]
We investigated the molecular mechanisms associated with the synergistic antitumor effects observed following treatment with lapatinib and sulforaphane, as well as the efficacy of interactions between lapatinib and sulforaphane in SGC-7901 and lapatinib-resistant SGC-7901 cells
Lapatinib-resistant SGC-7901 cells were developed by 24 h exposure of SGC-7901 cells to 1 μM concentrations of lapatinib. e primary antibodies against human epidermal growth factor receptor 2 (HER2), p-HER2, AKT, p-AKT, ERK, and p-ERK were bought from Cell Signaling Technology (Danvers, MA, United States)
Summary
Gastric cancer (GC) is one of the most common malignant tumors worldwide, with high morbidity and mortality [1]. The diagnosis and treatment methods of GC have greatly improved, the five-year survival rate of GC patient is still 10–30% [2]. The effects of lapatinib on gastric cancer (GC) remain to be clear. We aimed to investigate the therapeutic effects of lapatinib combined with sulforaphane on GC and its underlying mechanisms. SGC-7901 and lapatinib-resistant SGC-7901 cells were treated with lapatinib (0.2 μM), sulforaphane (5 μM), or their combinations. We observed that lapatinib combined with sulforaphane significantly decreased cell viability and inhibited cell migration of drug-sensitive and drug-resistant cells. Western blotting revealed that the expressions of HER-2, p-HER-2, AKT, p-AKT, ERK, and p-ERK were downregulated by lapatinib-sulforaphane treatment. Combination of lapatinib and sulforaphane might be a novel and promising therapeutic treatment for lapatinib-sensitive or lapatinib-resistant GC patients
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