PMID- 38062832 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240220 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 28 IP - 11 DP - 2023 Nov 29 TI - Aspirin Inhibits Brain Metastasis of Lung Cancer via Upregulation of Tight Junction Protein Expression in Microvascular Endothelial Cells. PG - 320 LID - 10.31083/j.fbl2811320 [doi] AB - BACKGROUND: The brain is one of the most vulnerable metastasis sites in lung cancer; approximately 40-50% of lung cancer patients develop brain metastasis during the disease course, contributing to the poor prognosis and high mortality of lung cancer patients. Therefore, it is important to clarify the molecular mechanism underlying brain metastasis of lung cancer for improving the overall survival of lung cancer patients. The present study aimed to investigate the potential role of blood-brain barrier (BBB) permeability in the development of brain metastasis of lung cancer and explore the effect of aspirin in an in-vitro BBB model. METHODS: An in-vitro BBB model was established. The expression of heat shock protein 70 (HSP 70), zonula occludens-1 (ZO-1), and occludin in rat brain microvascular endothelial cells was detected using Western blot at different time points following the administration of aspirin. RESULTS: HSP70, ZO-1, and occludin expressions did not show significant changes before aspirin administration, but increased noticeably after aspirin administration. Tumor necrosis factor-alpha (TNF-alpha) could significantly attenuate the increased expression of these proteins induced by aspirin. Additionally, TNF-alpha also significantly reversed the aspirin-induced decrease of BBB permeability. CONCLUSIONS: Aspirin may inhibit brain metastasis of lung cancer in a time-dependent manner via upregulating tight junction proteins to reduce BBB permeability, and this effect can be reversed by TNF-alpha. CI - (c) 2023 The Author(s). Published by IMR Press. FAU - Wei, Dianfang AU - Wei D AD - Department of Basic Medicine, Qilu Medical University, 255300 Zibo, Shandong, China. FAU - Tang, Ming AU - Tang M AD - Department of Basic Medicine, Qilu Medical University, 255300 Zibo, Shandong, China. FAU - Gong, Weibo AU - Gong W AD - Department of Basic Medicine, Qilu Medical University, 255300 Zibo, Shandong, China. FAU - Liu, Jingshuo AU - Liu J AD - Department of Basic Medicine, Qilu Medical University, 255300 Zibo, Shandong, China. FAU - Qin, Lijuan AU - Qin L AD - School of Basic Medical Sciences, North China University of Science and Technology, 063210 Tangshan, Hebei, China. LA - eng GR - 81101912/Natural Science Foundation of China/ GR - ZD20160082/Science and Technology Project for Colleges and Universities in Hebei Province/ GR - 20170901/Scientific Research Foundation of Hebei Health Department/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 0 (Tight Junction Proteins) RN - 0 (Occludin) RN - R16CO5Y76E (Aspirin) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Rats MH - Animals MH - Humans MH - Tight Junction Proteins/metabolism MH - Occludin/genetics/metabolism/pharmacology MH - Endothelial Cells/metabolism MH - Up-Regulation MH - *Lung Neoplasms/drug therapy/metabolism MH - Aspirin/pharmacology MH - Tumor Necrosis Factor-alpha/metabolism MH - Blood-Brain Barrier MH - *Brain Neoplasms/drug therapy/metabolism MH - Tight Junctions/metabolism OTO - NOTNLM OT - aspirin OT - blood-brain barrier OT - brain metastasis OT - lung cancer OT - tight junction protein COIS- The authors declare no conflict of interest. EDAT- 2023/12/08 06:42 MHDA- 2023/12/17 13:19 CRDT- 2023/12/08 03:43 PHST- 2022/09/06 00:00 [received] PHST- 2023/06/16 00:00 [revised] PHST- 2023/08/08 00:00 [accepted] PHST- 2023/12/17 13:19 [medline] PHST- 2023/12/08 06:42 [pubmed] PHST- 2023/12/08 03:43 [entrez] AID - S2768-6701(23)00997-8 [pii] AID - 10.31083/j.fbl2811320 [doi] PST - ppublish SO - Front Biosci (Landmark Ed). 2023 Nov 29;28(11):320. doi: 10.31083/j.fbl2811320.