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Abstract

Inhibition of Axl: Enhancement of Erlotinib Cytotoxicity in Human Pancreatic Cancer Cells

Author(s): Jun Wan, J. Cui, Shu Guang Jiao, S. Zhao, M. Liu, Q. T. Li, S. Y. Chen, Lei Wang and H. Ke*
Department of Pharmacy, 1Department of Oncology, The Third Clinical Medical College of China Three Gorges University, Gezhouba Central Hospital of Sinopharm, 2Department of Pathogenic Biology, School of Medicine, China Three Gorges University, Yichang, Hubei 443002, China

Correspondence Address:
H. Ke, Department of Oncology, The Third Clinical Medical College of China Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, Hubei 443002, China, E-mail: kh196651@163.com


To investigate the changes in sensitivity of pancreatic cancer cells to erlotinib after specific down-regulation of Axl (Anexelekto) expression and its mechanism is the objective of the study. The expression of Axl in pancreatic cancer cells was specifically down-regulated by small interfering ribonucleic acid technology and identified by Western blotting. The survival rate of pancreatic cancer cells under the effect of erlotinib at different concentrations (0, 2.5, 5, 10 and 20 μmol/l) was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The morphological changes of cell cycle were detected by flow cytometry and the expression of protein kinase B, phosphorylated protein kinase B, extracellular signal-regulated kinase and phosphorylated extracellular signal-regulated kinase were detected by immunoblotting. The expression of Axl was significantly inhibited at 24, 48 and 72 h after transfection with small interfering ribonucleic acid-Axl, with the most significant inhibitory effect at 48 h (p<0.05). Compared with human pancreatic cancer cell line, PANC-1/small interfering ribonucleic acid-control, erlotinib had significant proliferation inhibition and pro-apoptotic effect on human pancreatic cancer cell line, PANC-1/small interfering ribonucleic acid-Axl cells, and the difference was statistically significant (p<0.05). Compared with human pancreatic cancer cell line, PANC-1/small interfering ribonucleic acid-control, erlotinib significantly reduced the protein expression of phosphorylated extracellular signal-regulated kinase and phosphorylated protein kinase B in human pancreatic cancer cell line, PANC-1/small interfering ribonucleic acid-Axl cells (p<0.05), but total extracellular signal-regulated kinase and protein kinase B protein expression were not affected. Specific inhibition of Axl expression in pancreatic cancer cells enhances the sensitivity of pancreatic cancer cells to erlotinib by inhibiting phosphorylation of extracellular signal-regulated kinase and protein kinase B protein.

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