Zhang Lan, Xiao Xuyang, An Hui, Wang Jian, Ma Yanmei, Qian Yi-Hua
School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Department of Thoracic Surgery, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Oncol Rep. 2017 May;37(5):2913-2919. doi: 10.3892/or.2017.5524. Epub 2017 Mar 23.
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.
C-C趋化因子受体7（CCR7）的激活已被证明可介导非小细胞肺癌（NSCLC）的发生和发展。然而，CCR7抑制在NSCLC中的潜在治疗作用仍不清楚。因此，本研究旨在探讨CCR7抑制NSCLC A549细胞凋亡和上皮-间质转化（EMT）的分子机制。使用趋化因子配体21（CCL21）激活CCR7，结果显示CCR7上调抑制细胞凋亡并影响凋亡相关蛋白水平。然而，CCR7-siRNA处理显著促进凋亡并抑制炎症反应以及转化生长因子β1（TGF-β1）诱导的EMT。此外，CCR7-siRNA使NF-κB信号通路失活，并且通过其特异性拮抗剂吡咯烷二硫代氨基甲酸盐抑制NF-κB表明NF-κB参与CCR7介导的凋亡。总之，CCR7上调促进A549细胞增殖和炎症。总之，通过siRNA处理抑制CCR7可促进细胞凋亡并抑制炎症反应以及TGF-β1诱导的EMT，这可能与NF-κB信号通路有关。
