Cancer Management and Research (Jul 2020)
Knockdown of IKKβ Inhibits Tumor Development in a Leptomeningeal Metastasis Mouse Model and Proliferation of Lung Cancer Cells
Abstract
Yakun Liu,1,2,* Yuanyuan Li,1,2,* Zhongyao Li,1,2 Chunyan Li,1– 3 Junying He,1– 3 Hui Bu1– 3 1Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People’s Republic of China; 2Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei 050000, People’s Republic of China; 3Institute of Cardiocerebrovascular Disease, Shijiazhuang, Hebei 050000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui BuDepartment of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People’s Republic of ChinaTel/ Fax +86 13831106903Email [email protected]: This study will explore the role of IKKβ in the leptomeningeal metastasis (LM) of lung cancer cells.Methods: In vitro studies were conducted in mouse Lewis lung carcinoma (LLC) cells with IKKβ knockdown. Cell proliferation was explored using CCK-8 and tumor colony-forming assays. The expression of the extracellular signal-regulated kinase (ERK) signaling pathway was detected by Western blot. Tumor cell apoptosis was identified through Western blot detection of Bax and Bcl-2. The migration of tumor cells was identified by a wound healing assay. In vivo studies used an LM mouse model developed by injecting LLC cells with or without IKKβ knockdown into the cisterna magna. Mouse brain and spinal samples were sectioned for hematoxylin and eosin staining.Results: In vitro: IKKβ knockdown inhibits tumor cell proliferation, initiates apoptosis, and attenuates cell migration. In vivo: IKKβ knockdown inhibits tumor growth in the LM mouse model. In addition, the in vitro results showed that IKKβ knockdown attenuated the expression of ERK phosphorylation in LLC cells.Conclusion: Blocking the NF-κB signaling pathway by IKKβ knockdown in LLC cells inhibited tumor growth in the LM mouse model. IKKβ supports leptomeningeal tumor progression by promoting cancer cell proliferation and migration and inhibiting cancer cell apoptosis, and these actions may be correlated to ERK signaling.Keywords: leptomeningeal metastasis, non-small-cell lung cancer, NF-κB signaling, IKKβ, shRNA
