Knockdown of IKKβ Inhibits Tumor Development in a Leptomeningeal Metastasis Mouse Model and Proliferation of Lung Cancer Cells.

Objective: This study will explore the role of IKK beta in the leptomeningeal metastasis (LM) of lung cancer cells. Methods: In vitro studies were conducted in mouse Lewis lung carcinoma (LLC) cells with IKK beta 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 IKK beta knockdown into the cisterna magna. Mouse brain and spinal samples were sectioned for hematoxylin and eosin staining. Results: In vitro: IKK beta knockdown inhibits tumor cell proliferation, initiates apoptosis, and attenuates cell migration. In vivo: IKK beta knockdown inhibits tumor growth in the LM mouse model. In addition, the in vitro results showed that IKK beta knockdown attenuated the expression of ERK phosphorylation in LLC cells. Conclusion: Blocking the NF-kappa B signaling pathway by IKK beta knockdown in LLC cells inhibited tumor growth in the LM mouse model. IKK beta 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.