Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells.

Abstract

Gastric Cancer (GC) is currently one of the major malignancies that threaten human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert antitumor effects. However, its function in gastric cancer is incompletely understood. The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with Dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. Proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the Cell Counting Kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken Chorioallantoic Membrane (CAM) assays. Proliferation- associated protein (Ki67), apoptosis-related protein (Bcl-2), and Vascular Endothelial Growth Factor A (VEGF-A) were quantified by Western blotting. The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with control and either drug alone. The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.