title: Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells: Importance of ERK1/2 and AKT Signaling Pathways.
abstract: Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR). In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3' -kinase(PI3K)-Akt (PI3K/AKT) phosphorylation were determined by Western blot analysis. Human embryonic lung fibroblast 2BS and lung cancer NCI-H446 cell lines were irradiated with LDR at different doses (20-100 mGy). In response to 20 to 75 mGy X-rays, cell proliferation was significantly increased in 2BS but not in NCI-H446 cells. In 2BS cells, LDR at 20 to 75 mGy also stimulated phosphorylation of MAPK/ERK pathway proteins including ERK, MEK, and Raf and of the PI3K/AKT pathway protein AKT. To test whether ERK1/2 and AKT pathway activation was involved in the stimulation of cell proliferation in 2BS cells, the MAPK/ERK and PI3K/AKT pathways were inhibited using their specific inhibitors, U0126 and LY294002. U0126 decreased the phosphorylation of ERK1/2, and LY294002 decreased the phosphorylation of AKT; each could significantly inhibit LDR-induced 2BS cell proliferation. However, LDR did not stimulate these kinases, and kinase inhibitors also did not affect cell proliferation in the NCI-H446 cells. These results suggest that LDR stimulates cell proliferation via the activation of both MAPK/ERK and PI3K/AKT signaling pathways in 2BS but not in NCI-H446 cells. This finding implies the potential for applying LDR to protect normal tissues from radiotherapy without diminishing the efficacy of tumor therapy.
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China; Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA.
authors.forename: Junlian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Dehai
authors.initials: D
authors.lastname: Yu
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA.
authors.forename: Shirong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Tianjin Key Lab of Radiation and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville, Louisville, KY, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
keywords: cell proliferation; hormesis; ionizing radiation; low dose