ANTITUMOR EFFECTS OF ANLOTINIB HYDROCHLORIDE ON HUMAN PANCREATIC CANCER CELLS

Anlotinib hydrochloride (AL3818), a new multi-kinase inhibitor, has shown promising antitumor efficiency in several advanced malignancies. However, data on AL3818 use for pancreatic cancer are still limited. This study aimed to investigate the antitumor activity of AL3818 and its underlying molecular mechanisms in human pancreatic cancer cells. The human pancreatic cancer cell line PANC-1 was exposed in vitro to increasing concentrations of AL3818 treatment (0.1, 0.5, 1, 2, or 5 ??mol/L). The antiproliferative effect of AL3818 was determined by 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell cycle alterations and apoptosis rates were evaluated by flow cytometry, while expression of Tolllike receptor 4 (TLR-4), Nuclear factor kappa B (NF-??B), Vascular endothelial growth factor (VEGF), survivin, and Bax proteins were detected by Western blot. Our experimental data demonstrated a dose-dependent decrease in the proliferation of PANC-1 cells following treatment with AL3818. AL3818 efficiently induced G2/M phase cell cycle arrest and promoted cell apoptosis in a dose-dependent manner. In addition, expression levels of TLR-4, NF-??B, VEGF, and survivin proteins were decreased, while upregulation of Bax levels was achieved under AL3818 treatment. Our results suggested that AL3818 could interfere with PANC-1 cell proliferation and apoptosis in vitro. Treatment was also found to induce G2/M phase cell cycle arrest, possibly associated with upregulation of Bax protein and downregulation of VEGF, survivin, and TLR-4/NF-??B signalling pathway. Further research is clearly warranted to confirm these findings.