Inhibition of CCR7 promotes NF-κB-dependent apoptosis and suppresses epithelial-mesenchymal transition in non-small cell lung cancer.
Activation of C-C chemokine receptor type 7 (CCR7) has been demonstrated to mediate the occurrence and progression of non-small cell lung cancer (NSCLC). However, the potential therapeutic role of CCR7 inhibition in NSCLC is still obscure. Thus, the present study was conducted to investigate the molecular mechanism underlying the inhibition of CCR7 on cell apoptosis and epithelial-mesenchymal transition (EMT) in NSCLC A549 cells. Chemokine ligand 21 (CCL21) was used to activate CCR7 and the results revealed that CCR7 upregulation inhibited cell apoptosis and affected apoptosis‑related protein levels. However, CCR7-siRNA treatment markedly promoted apoptosis and suppressed inflammatory response and transforming growth factor β1 (TGF-β1)-induced EMT. In addition, CCR7‑siRNA inactivated the NF-κB signaling pathway and inhibition of NF-κB via its specific antagonist, pyrrolidine dithiocarbamate, indicated that NF-κB was involved in the CCR7-mediated apoptosis. In conclusion, upregulation of CCR7 promoted cell proliferation and inflammation in A549 cells. In conclusion, inhibition of CCR7 via siRNA treatment promoted cell apoptosis and suppressed the inflammatory response and TGF-β1‑induced EMT, which may be associated with NF-κB signaling.
School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Lan
L
Zhang
Department of Thoracic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Xuyang
X
Xiao
Department of Cardiothoracic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Hui
H
An
Department of Neurological Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Jian
J
Wang
Department of Nursing, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Yanmei
Y
Ma
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Yi-Hua
YH
Qian
D000072283:A549 Cells; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation
C515370:CCR7 protein, human; D054421:Chemokine CCL21; D016328:NF-kappa B; D034741:RNA, Small Interfering; D054400:Receptors, CCR7; D053773:Transforming Growth Factor beta1