文献类型：期刊文献

英文题名：Inhibition of primary ciliogenesis enhances efficacy of EGFR-TKIs against non-small cell lung cancer cells

作者：Jin, Liangliang[1];Wei, Li[2];Hua, Junrui[3];Zhang, Rong[4,5];Chen, Jiaxin[4,5];He, Jinpeng[3];Yang, Yanli[1]

第一作者：Jin, Liangliang

通信作者：Yang, YL[1];He, JP[2]

机构：[1]940th Hosp Joint Logist Support Force Chinese Peop, Dept Pathol, 333 South Binhe Rd, Lanzhou 730050, Gansu, Peoples R China;[2]Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[3]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu, 509 Nanchang Rd, Lanzhou 73000, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[5]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou 730000, Gansu, Peoples R China

第一机构：940th Hosp Joint Logist Support Force Chinese Peop, Dept Pathol, 333 South Binhe Rd, Lanzhou 730050, Gansu, Peoples R China

通信机构：[1]corresponding author), 940th Hosp Joint Logist Support Force Chinese Peop, Dept Pathol, 333 South Binhe Rd, Lanzhou 730050, Gansu, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu, 509 Nanchang Rd, Lanzhou 73000, Gansu, Peoples R China.

年份：2026

卷号：55

期号：2

外文期刊名：ONCOLOGY REPORTS

收录：;Scopus(收录号：2-s2.0-105023911865);WOS:【SCI-EXPANDED(收录号:WOS:001642323900001)】；

基金：The authors would like to thank Dr Dan Xu and Dr Qingfeng Wu (Biomedical Platform of the Public Technology Center, Institute of Modern Physics, Chinese Academy of Sciences) for providing technical assistance in flow cytometric analysis.

语种：英文

外文关键词：non-small cell lung cancer; epidermal growth factor receptor-tyrosine kinase inhibitors; primary cilia; adenylate cyclase 3

摘要：Primary cilia are antenna-like organelles on almost all human cells that sense and transduce extracellular cues into cellular response. Primary cilia have been reported to be implicated in drug resistance in several cancer types, but their roles in cellular response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are still not fully understood. In the present study, it was reported that primary cilia are more prevalent in EGFR-TKI-insensitive A549 and H23 cells compared with the drug-sensitive HCC827 and PC9 cells by immunofluorescence staining assay. Importantly, treatment with EGFR-TKIs (gefitinib and dacomitinib) results in a dose-dependent increase in cilia number and length in A549 and H23 cells, an effect not observed in HCC827 and PC9 cells. Upon administration of gefitinib, A549 cells predominantly arrest in the G1 phase detected by flow cytometric analysis, with a minority undergoing cell death and the majority entering senescence. Inhibition of ciliogenesis through the knockdown of IFT88 or ARL13B by targeted small interfering RNAs markedly enhances the sensitivity of A549 cells to EGFR-TKIs by promoting a shift from senescence to cell death. Furthermore, it was demonstrated by immunoblotting and immunofluorescence colocalization analysis that both the expression and ciliary localization of adenylate cyclase 3 (AC3) are significantly upregulated following EGFR-TKIs treatment, and the reduction of AC3 expression effectively mitigates cellular drug resistance in A549 cells. These findings highlight a critical role for the cilia-AC3 axis in modulating cellular response to EGFR-TKIs, suggesting it as a potential therapeutic target for the treatment of NSCLC.