Antitumor Efficacy and Mechanisms of Lapatinib in Combination with Cisplatin on Esophageal Squamous Cancer Cells

Abstract

Objective To evaluate the antitumor efficacy of lapatinib in combination with cisplatin on esophageal squamous cell carcinoma (ESCC) and related mechanisms. Methods Combined effects of lapatinib and cisplatin on the proliferation of ESCC cells were measured by MTT assay, and the combination index values were calculated by Chou-Talalay method. PI staining assay and Annexin V-FITC/PI staining assay were used to analyze the cell cycle arrest and cell apoptosis after the treatment with lapatinib, cisplatin and lapatinib plus cisplatin. The activation of EGFR and HER2 as well as downstream signaling molecules were detected by Western blot. Results The combination of lapatinib and cisplatin showed synergistic inhibitory effect on the proliferation of ESCC cells with the combination index (CI) values less than 1. Lapatinib in combination with cisplatin blocked cell cycle at G2/M phase, and induced significantly the apoptosis of ESCC cells. The underlying mechanisms of potentiated effects of combined treatment were associated with reduced phosphorylation of EGFR and HER2 and the downstream signaling molecules AKT and ERK. Conclusion The combination of lapatinib and cisplatin play synergistic antitumor effects on ESCC in vitro, suggesting that their combination is one of the promising treatment strategies for ESCC patients with EGFR and HER2 overexpression.

Keywords

• lapatinib
• cisplatin
• esophageal squamous cell carcinoma
• egfr
• her2