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Potential mechanism of interleukin‐8 production from lung cancer cells: An involvement of EGF–EGFR–PI3K–Akt–Erk pathway
Author(s) -
Zhang Yong,
Wang Linyan,
Zhang Miaomiao,
Jin Meiling,
Bai Chunxue,
Wang Xiangdong
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22722
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , cancer research , mapk/erk pathway , erlotinib , lung cancer , tumor microenvironment , medicine , cancer , cancer cell , phosphorylation , signal transduction , immunology , biology , epidermal growth factor receptor , microbiology and biotechnology , tumor cells
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. J. Cell. Physiol. 227: 35–43, 2012. © 2011 Wiley Periodicals, Inc.