title: Potential mechanism of interleukin-8 production from lung cancer cells: an involvement of EGF-EGFR-PI3K-Akt-Erk pathway.
abstract: Tumor inflammatory microenvironment is considered to play the role in the sensitivity of tumor cells to therapies and prognosis of lung cancer patients. Interleukin-8 (IL-8) is one of critical chemo-attractants responsible for leukocyte recruitment, cancer proliferation, and angiogenesis. The present study aimed at investigating potential mechanism of IL-8 production from human non-small cell lung cancer (NSCLC) SPC-A1 cells. We initially found that EGF could directly stimulate IL-8 production, proliferation, and bio-behaviors of lung cancer cells through the activation of EGFR, PI3K, Akt, and Erk signal pathway. EGF-stimulated IL-8 production, phosphorylation of Akt and Erk, and cell proliferation and movement could be inhibited by EGFR inhibitor (Erlotinib), PI3K inhibitor (GDC-0941 BEZ-235 and SHBM1009), and ERK1/2 inhibitor (PD98059). Our data indicate that IL-8 production from lung cancer cells could be initiated by their own produced factors, leading to the recruitment of inflammatory cells in the cancer tissue, and the formation of inflammatory microenvironment. Thus, it seems that the signal pathway of EGFR-PI3K-Akt-Erk can be the potential target of therapies for inflammatory microenvironment in lung cancer.
authors.affiliation: Department of Pulmonary Medicine, Center for Biomedical Research, Zhongshan Hospital, Fudan University Medical School, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Linyan
authors.initials: L
authors.lastname: Wang
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Zhang
authors.forename: Meiling
authors.initials: M
authors.lastname: Jin
authors.forename: Chunxue
authors.initials: C
authors.lastname: Bai
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors