H Wei1, F Li, P Fu, X Liu. 1. Department of General Surgery, First Affiliated Hospital, and Zhejiang University School of Medicine, Zhejiang Province, China. whycherry77@hotmail.com
Abstract
BACKGROUND: Hypoxia plays a crucial role in the development of solid tumors. Hypoxia-inducible factor-1alpha (HIF-1alpha) is essential for this process, and has been suggested to be a target for cancer therapy. New therapeutic approaches for pancreatic cancer are needed owing to the extremely poor prognosis, in large part as a consequence of high rates of metastasis. The mechanism remains to be explored. AIM: To illustrate the role of hypoxia-inducible factor-1alpha in pancreatic cancer metastasis and the value of the molecule as a target for pancreatic cancer therapy. MATERIALS AND METHODS: To address this shortcoming, we used both in vitro and in vivo approaches to evaluate the overall effects of HIF-1alpha on pancreatic cancer. We used a plasmid encoding small interfering RNAs (SiRNAs) to silence HIF-1alpha expression in the Panc-1 pancreatic cancer cell line, and used a series of assays to detect changes in gene expression at the protein and mRNA levels, cell proliferation, cell apoptosis, and the abilities of cells to migrate under both hypoxia and normoxia conditions. RESULTS: Both in vitro and in vivo analysis suggested that hypoxia significantly promotes cell proliferation and migration, resulting in metastasis. Pancreatic cancer cells in which HIF-1alpha expression was inhibited were less invasive, with reduced resistance to hypoxia, impaired migration, and reduced capacity to cause metastasis. CONCLUSIONS: HIF-1alpha may be a dominant factor driving the metastatic progression of pancreatic cancer and can be a potent therapeutic target for the disease.
BACKGROUND:Hypoxia plays a crucial role in the development of solid tumors. Hypoxia-inducible factor-1alpha (HIF-1alpha) is essential for this process, and has been suggested to be a target for cancer therapy. New therapeutic approaches for pancreatic cancer are needed owing to the extremely poor prognosis, in large part as a consequence of high rates of metastasis. The mechanism remains to be explored. AIM: To illustrate the role of hypoxia-inducible factor-1alpha in pancreatic cancer metastasis and the value of the molecule as a target for pancreatic cancer therapy. MATERIALS AND METHODS: To address this shortcoming, we used both in vitro and in vivo approaches to evaluate the overall effects of HIF-1alpha on pancreatic cancer. We used a plasmid encoding small interfering RNAs (SiRNAs) to silence HIF-1alpha expression in the Panc-1 pancreatic cancer cell line, and used a series of assays to detect changes in gene expression at the protein and mRNA levels, cell proliferation, cell apoptosis, and the abilities of cells to migrate under both hypoxia and normoxia conditions. RESULTS: Both in vitro and in vivo analysis suggested that hypoxia significantly promotes cell proliferation and migration, resulting in metastasis. Pancreatic cancer cells in which HIF-1alpha expression was inhibited were less invasive, with reduced resistance to hypoxia, impaired migration, and reduced capacity to cause metastasis. CONCLUSIONS:HIF-1alpha may be a dominant factor driving the metastatic progression of pancreatic cancer and can be a potent therapeutic target for the disease.
Authors: Lauren E Colbert; Sarah B Fisher; Serdar Balci; Burcu Saka; Zhengjia Chen; Sungjin Kim; Bassel F El-Rayes; N Volkan Adsay; Shishir K Maithel; Jerome C Landry; Walter J Curran Journal: Int J Radiat Oncol Biol Phys Date: 2015-01-13 Impact factor: 7.038