Cancer research, 2020, 03-01, Volume: 80, Issue:5
Cell membrane transporters facilitate the passage of nucleobases and nucleosides for nucleotide synthesis and metabolism, and are important for the delivery of nucleoside analogues used in anticancer drug therapy. Here, we investigated if cell membrane transporters are involved in the cellular uptake of the nucleoside analogue DNA damage mediator 6-thio-2'-deoxyguanosine (6-thio-dG). A large panel of non-small cell lung cancer (NSCLC) cell lines (73 of 77) were sensitive to 6-thio-dG; only four NSCLC lines were resistant to 6-thio-dG. When analyzed by microarray and RNA sequencing, the resistant NSCLC cell lines clustered together, providing a molecular signature for patients that may not respond to 6-thio-dG. Significant downregulation of solute carrier family 43 A3 ( Topics: Adenocarcinoma of Lung; Amino Acid Transport Systems; Animals; Biomarkers, Tumor; Cell Line, Tumor; Deoxyguanosine; DNA Damage; Down-Regulation; Drug Resistance, Neoplasm; Female; Gene Knockdown Techniques; Humans; Kaplan-Meier Estimate; Lung; Lung Neoplasms; Mice; RNA, Small Interfering; Telomere; Thionucleosides; Xenograft Model Antitumor Assays | 2020 |