title: The role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma cell line PC-9 induced by icotinib.
abstract: OBJECTIVE
  The aim of this study is to estimate the role of JAK/STAT3 signaling pathway on apoptosis of lung adenocarcinoma induced by icotinib.
  
  
  METHODS
  EGFR mutation was detected in lung adenocarcinoma cell line PC-9 by ARMS assay; The inhibitory rates of cell proliferation of PC-9 cells which were exposed to different concentrations of icotinib (0~100 μMol/L) for different time (24~72 h) respectively were evaluated by MTT assay; Apoptosis of PC-9 cells exposed to different concentrations of icotinib (0, 0.1, 1 and 10 μMol/L) for 48 h were evaluated by TUNEL assay; JAK2, STAT3, Bcl-2, Bax mRNA expressions were evaluated by Real-time PCR assay; The protein levels of P-STAT3 and IL-6 were evaluated by Western-blot assay.
  
  
  RESULTS
  Human lung adenocarcinoma cell line PC-9 had an exon 19 deletion mutation in EGFR gene; Followed by treatment of icotinib, the proliferation of PC-9 cells were all inhibited significantly, especially in 48 and 72 h (P<0.01) in all concentrations; The inhibitory rates of cell proliferation in different treating time had statistical significance (P<0.01); Cell apoptosis in different concentrations were increased significantly (P<0.05); Along with the increasing concentrations, gene expression levels of JAK2, STAT3 and Bcl-2 decreased significantly (P<0.05), Bax increased significantly (P<0.05), JAK2/STAT3 ratios increased significantly (P<0.01), and Bcl-2/bax ratios decreased significantly (P<0.01); P-STAT3 and IL-6 protein levels were inhibited significantly in higher concentration.
  
  
  CONCLUSIONS
  JAK/STAT3 signaling pathway participates in apoptosis of PC-9 cells induced by icotinib. The most likely mechanism is icotinib inhibited the gene expression levels of JAK2, STAT3 and Bcl-2, so with the P-STAT3 and IL-6 protein levels, and mediated gene Bax overexpression.
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Zongjuan
authors.initials: Z
authors.lastname: Ming
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Na
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Zequn
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Toracic Surgery Section, Department of Surgery, University of Michigan Ann Arbor, Michigan 48109, USA.
authors.forename: Guo'an
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University Xi'an 710004, China.
authors.forename: Shuanying
authors.initials: S
authors.lastname: Yang
keywords: Icotinib; JAK/STAT3 signaling pathway; apoptosis; lung adenocarcinoma