机构：[1]Department of Thoracic Surgery, The First Affiliated Hospital of GuangzhouMedical University, Guangzhou Research Institute of Respiratory Disease,China Key Laboratory of Respiratory Disease, National Center for Clinical Trialson Respiratory Diseases, No .151 Yanjiangxi Road, Guangzhou, Guangdong510120, China[2]The Central Hospital of Shaoyang City, Shaoyang, Hu’nan,China[3]Affiliated Cancer Hospital & Institute of Guangzhou Medical University,Guangzhou, China[4]Department of Thoracic Surgery, Dongguan People’sHospital, Dongguan, Guangdong, China[5]State Key Laboratory of QualityResearch in Chinese Medicine, Macau Institute for Applied Research in Medicineand Health, Macau University of Science and Technology, Macau, SAR,China[6]Department of Pathology, The First Affiliated Hospital of GuangzhouMedical University, Guangzhou, China
Cancer cells are characterized by aberrant activation of lipid biosynthesis, producing saturated fatty acids and monounsaturated fatty acids via stearoyl-CoA desaturases (SCD) for regulating metabolic and signaling platforms. SCD1 overexpression functions as an oncogene in lung cancer and predicts a poor clinical outcome. This study aimed to investigate the role of SCD1 inhibition by EGFR inhibitor (Gefitinib)-based anti-tumor therapy of lung cancer both in vitro and in vivo.
CCK-8 assay was performed to determine cell viability. The SCD1 mRNA level was detected by qPCR. The protein levels were assessed by Western blotting. E-cadherin and N-cadherin levels were determined by immunofluorescence. Apoptosis detection was conducted by flow cytometry. Cell migration or invasion was evaluated by transwell assay. The tumor sizes and tumor volumes were calculated in nude mice by subcutaneous injection of A549 cells transfected with vector of pcDNA3.1-SCD1 or negative control. Expression of Ki-67 was detected by immunohistochemistry.
SCD1 up-regulated expression was observed in lung cancer cell lines. Cells with overexpressed SCD1 had high IC50 values for Gefitinib in A549 and H1573 cell lines. Overexpression of SCD1 inhibited Gefitinib-induced apoptosis, decreased cell vitality and impaired ability of migration and invasion, while these effects were counteracted by A939572. Mechanistically, SCD1 promoted the activation of proliferation and metastasis-related EGFR/PI3K/AKT signaling, and up-regulated epithelial to mesenchymal transition (EMT) phenotype in the two cell lines, which was restored by SCD1 inhibition. Furthermore, in spite of EGFR inhibition, overexpression of SCD1 in vivo significantly promoted tumor growth by activating EGFR/PI3K/AKT signaling in tumor tissues, but A939572 treatment restricted SCD1-induced tumor progression and inhibited EMT phenotype of cancer cells in vivo.
These findings indicated that inhibition of oncogene SCD1 is required for targeting EGFR therapy in lung cancer.
基金：
the Ph.D. Start-up Fund of Natural Science
Foundation of Guangdong Province, China (2017A030310153); Foundation of
bureau of education of Guangzhou for scientific research in Universities and
Colleges of Guangzhou, China (1201630163); Science and Technology Program
of health and Family planning Commission of Guangzhou Municipality
(2017A013010097); the Ph.D. Start-up Fund of Natural Science Foundation of
Guangdong Province, China (2016A030310273).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|3 区医学
小类|3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|3 区肿瘤学
第一作者：
第一作者机构：[1]Department of Thoracic Surgery, The First Affiliated Hospital of GuangzhouMedical University, Guangzhou Research Institute of Respiratory Disease,China Key Laboratory of Respiratory Disease, National Center for Clinical Trialson Respiratory Diseases, No .151 Yanjiangxi Road, Guangzhou, Guangdong510120, China[2]The Central Hospital of Shaoyang City, Shaoyang, Hu’nan,China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
She Kelin,Fang Shenghua,Du Wei,et al.SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals.[J].Cancer cell international.2019,19:103.doi:10.1186/s12935-019-0809-y.
APA：
She Kelin,Fang Shenghua,Du Wei,Fan Xingxing,He Jiaxi...&Huang Jun.(2019).SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals..Cancer cell international,19,
MLA：
She Kelin,et al."SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals.".Cancer cell international 19.(2019):103
