https://scholars.lib.ntu.edu.tw/handle/123456789/495016
標題: | Rhodomycin A, a novel Src-targeted compound, can suppress lung cancer cell progression via modulating Src-related pathways | 作者: | Lai Y.-H. Chen M.-H. Lin S.-Y. Lin S.-Y. Wong Y.-H. SUNG-LIANG YU HUEI-WEN CHEN CHIH-HSIN YANG Chang G.-C. Chen J.J.W. |
公開日期: | 2015 | 出版社: | Impact Journals LLC | 卷: | 6 | 期: | 28 | 起(迄)頁: | 26252-26265 | 來源出版物: | Oncotarget | 摘要: | Src activation is involved in cancer progression and the interplay with EGFR. Inhibition of Src activity also represses the signalling pathways regulated by EGFR. Therefore, Src has been considered a target molecule for drug development. This study aimed to identify the compounds that target Src to suppress lung cancer tumourigenesis and metastasis and investigate their underlying molecular mechanisms. Using a molecular docking approach and the National Cancer Institute (NCI) compound dataset, eight candidate compounds were selected, and we evaluated their efficacy. Among them, rhodomycin A was the most efficient at reducing the activity and expression of Src in a dose-dependent manner, which was also the case for Src-associated proteins, including EGFR, STAT3, and FAK. Furthermore, rhodomycin A significantly suppressed cancer cell proliferation, migration, invasion, and clonogenicity in vitro and tumour growth in vivo. In addition, rhodomycin A rendered gefitinib-resistant lung adenocarcinoma cells more sensitive to gefitinib treatment, implying a synergistic effect of the combination therapy. Our data also reveal that the inhibitory effect of rhodomycin A on lung cancer progression may act through suppressing the Src-related multiple signalling pathways, including PI3K, JNK, Paxillin, and p130cas. These findings will assist the development of anti-tumour drugs to treat lung cancer. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84944474759&doi=10.18632%2foncotarget.4761&partnerID=40&md5=2e0036cc2f0a73021b9e6043902e1f87 https://scholars.lib.ntu.edu.tw/handle/123456789/495016 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.4761 | SDG/關鍵字: | Crk associated substrate protein; epidermal growth factor receptor; focal adhesion kinase; gefitinib; mitogen activated protein kinase; paxillin; phosphatidylinositol 3 kinase; protein tyrosine kinase; rhodomycin A; STAT3 protein; stress activated protein kinase; anthracycline; antineoplastic agent; antineoplastic antibiotic; protein kinase inhibitor; protein tyrosine kinase; quinazoline derivative; rhodomycin; animal cell; animal experiment; animal model; Article; cancer cell; cell invasion; cell migration; cell proliferation; cell viability; clonogenesis; colony formation; controlled study; cytotoxicity; dose response; drug mechanism; drug potency; drug potentiation; enzyme activity; enzyme inhibition; gene repression; human; human cell; in vitro study; in vivo study; information processing; lung cancer; lung carcinogenesis; lung metastasis; molecular docking; mouse; nonhuman; protein degradation; protein expression; protein targeting; tumor growth; adenocarcinoma; animal; antagonists and inhibitors; cell motion; chemical structure; chemistry; computer aided design; drug design; drug effects; drug resistance; drug screening; enzymology; genetics; Lung Neoplasms; metabolism; molecularly targeted therapy; pathology; SCID mouse; signal transduction; structure activity relation; time factor; tumor cell line; tumor invasion; Adenocarcinoma; Animals; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cell Movement; Cell Proliferation; Computer-Aided Design; Dose-Response Relationship, Drug; Drug Design; Drug Resistance, Neoplasm; Drug Synergism; Humans; Lung Neoplasms; Mice, SCID; Molecular Docking Simulation; Molecular Structure; Molecular Targeted Therapy; Neoplasm Invasiveness; Protein Kinase Inhibitors; Quinazolines; Signal Transduction; src-Family Kinases; Structure-Activity Relationship; Time Factors; Xenograft Model Antitumor Assays |
顯示於: | 腫瘤醫學研究所 |
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