並列タイトル等PARP阻害剤と5-アザデオキシシチジンの併用によるがん細胞への細胞傷害性増強とその転写プロファイルの違いについて
授与機関名Nagasaki University (長崎大学)
一般注記Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair and chromatin regulation. 5-Aza-2′-deoxycytidine (5-aza-dC) inhibits DNA methyltransferases, induces hypomethylation, blocks DNA replication, and causes DNA single strand breaks (SSBs). As the PARP inhibitor is expected to affect both DNA repair and transcriptional regulations, we investigated the effect of combinational use of PARP inhibitors on cytotoxicity of 5-aza-dC in human cancer cell lines. The combinational treatment of 5-aza-dC and PARP inhibitor PJ-34 exhibited a stronger cytotoxicity compared with their treatment alone in blood cancer HL-60, U937, and colon cancer HCT116 and RKO cells. Treatment with 5-aza-dC but not PJ-34 caused SSBs in HCT116 cell lines. Global genome DNA demethylation was observed after treatment with 5-aza-dC but not with PJ-34. Notably, in microarray analysis, combinational treatment with PJ-34 and 5-aza-dC caused dissimilar broad changes in gene expression profiles compared with their single treatments in both HCT116 and RKO cells. The profiles of reactivation of silenced genes were also different in combination of PJ-34 and 5-aza-dC and their single treatments. The results suggest that the combinational use of 5-aza-dC and PARP inhibitor may be useful by causing distinct transcriptional profile changes.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1471号 学位授与年月日:令和4年12月7日
Author: Tomonori Araki, Kensuke Hamada, Aung Bhone Myat, Hideki Ogino, Kohei Hayashi, Miho Maeda, Ying Tong, Yasufumi Murakami, Kazuhiko Nakao and Mitsuko Masutani
Citation: Cancers, 14(17), art.no. 4171; 2022
identifier:Nagasaki University (長崎大学), 博士(医学) (2022-12-07)
http://hdl.handle.net/10069/00041978
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