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Spinosad blocks CHRNA5 mediated EGFR signaling pathway activation to inhibit lung adenocarcinoma proliferation

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机构： [1]College of Life Science, Sichuan Normal University, Chengdu, Sichuan 610101, China [2]Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China [3]Zhuji People’s Hospital Affiliated to Wenzhou Medical University, Zhuji, Zhejiang 311899, China d [4]Hangzhou Medical College, Hangzhou, Zhejiang 310059, China

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关键词： LUAD nAChR Spinosad CHRNA5 EGFR

摘要：

Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide, with high incidence and low survival rates. Nicotinic acetylcholine receptors play an important role in the progression of LUAD. In this study, a screening of 17 nicotinic acetylcholine receptor allosteric agents revealed that spinosad effectively suppressed the proliferation of LUAD cells. The experiments demonstrated that spinosad induced cell cycle arrest in the G1 phase and stimulated apoptosis, thereby impeding the growth of LUAD and enhancing the responsiveness to gefitinib in vitro and vivo. Mechanistic insights obtained through transcriptome sequencing, Co-IP, and protein immunoblots indicated that spinosad disrupted the interaction between CHRNA5 and EGFR, thereby inhibiting the formation of downstream complexes and activation of the EGFR signaling pathway. The supplementation of exogenous acetylcholine showed to mitigate the inhibition of LUAD cell proliferation induced by spinosad. This study elucidates the therapeutic effects and mechanisms of spinosad in LUAD, and offers a theoretical and experimental foundation for novel LUAD treatments.Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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大类 | 2 区

医学

小类 | 1 区药学 2 区医学：研究与实验

第一作者：

第一作者机构： [1]College of Life Science, Sichuan Normal University, Chengdu, Sichuan 610101, China [2]Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China

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通讯作者：

通讯机构： [2]Cancer Institute of Integrative Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China [4]Hangzhou Medical College, Hangzhou, Zhejiang 310059, China

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Spinosad blocks CHRNA5 mediated EGFR signaling pathway activation to inhibit lung adenocarcinoma proliferation

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