title: CCL21/CCR7 prevents apoptosis via the ERK pathway in human non-small cell lung cancer cells.
abstract: Previously, we confirmed that C-C chemokine receptor 7 (CCR7) promotes cell proliferation via the extracellular signal-regulated kinase (ERK) pathway, but its role in apoptosis of non-small cell lung cancer (NSCLC) cell lines remains unknown. A549 and H460 cells of NSCLC were used to examine the effect of CCL21/CCR7 on apoptosis using flow cytometry. The results showed that activation of CCR7 by its specific ligand, exogenous chemokine ligand 21 (CCL21), was associated with a significant decline in the percent of apoptosis. Western blot and real-time PCR assays indicated that activation of CCR7 significantly caused upregulation of anti-apoptotic bcl-2 and downregulation of pro-apoptotic bax and caspase-3, but not p53, at both protein and mRNA levels. CCR7 small interfering RNA significantly attenuated these effects of exogenous CCL21. Besides, PD98059, a selective inhibitor of MEK that disrupts the activation of downstream ERK, significantly abolished these effects of CCL21/CCR7. Coimmunoprecipitation further confirmed that there was an interaction between p-ERK and bcl-2, bax, or caspase-3, particularly in the presence of CCL21. These results strongly suggest that CCL21/CCR7 prevents apoptosis by upregulating the expression of bcl-2 and by downregulating the expression of bax and caspase-3 potentially via the ERK pathway in A549 and H460 cells of NSCLC.
authors.affiliation: Department of Pathology, the First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
authors.forename: Zihui
authors.initials: Z
authors.lastname: Liu
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Zixuan
authors.initials: Z
authors.lastname: Li
authors.forename: Wenting
authors.initials: W
authors.lastname: Luo
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation; D019254:Genes, bcl-2; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3