Kwon Hae-Won, An Jusung, Kim Jong Seung, Kang In-Cheol
Department of Bioconvergence System, Graduate School, and BioChip Research Center, Hoseo University, Asan, 336-795, South Korea.
Department of Chemistry, Korea University, Seoul, 02841, South Korea.
Biochem Biophys Rep. 2023 Jul 23;35:101517. doi: 10.1016/j.bbrep.2023.101517. eCollection 2023 Sep.
The goal of this paper was to look into the anti-tumor mechanism of Non-Steroidal Anti-Inflammatory Drug (NSAID)-conjugated SN-38 Prodrug in A549 lung cancer cells. We found that Indomethacine-SN-38 (IndoSN-38) and Naproxen-SN-38(NaproSN-38) as a theranostic prodrug targeting cyclooxygenase-2(COX-2) in cancer cells inhibited A549 cell viability in a dose-dependent fashion. IndoSN-38 and NaproSN-38 inhibited A549 cell viability in a dose-dependent fashion. The suppression of A549 cell viability was due to induction of the cell apoptosis by enhancing the activities of Caspase 3 and Caspase 8. The cell cycle arrest of sub-G1 was found in the cells treated with IndoSN-38 or NaproSN-38. Collectively, these data suggested that the anti-proliferative activities of the NSAID-conjugated SN-38 prodrugs were due to promotion of cell death and arresting the cell cycle which was similar with those of SN-38.
本文的目的是研究非甾体抗炎药（NSAID）共轭SN-38前药在A549肺癌细胞中的抗肿瘤机制。我们发现，吲哚美辛-SN-38（IndoSN-38）和萘普生-SN-38（NaproSN-38）作为靶向癌细胞中环氧化酶-2（COX-2）的治疗诊断前药，以剂量依赖的方式抑制A549细胞活力。IndoSN-38和NaproSN-38以剂量依赖的方式抑制A549细胞活力。A549细胞活力的抑制是由于通过增强半胱天冬酶3和半胱天冬酶8的活性诱导细胞凋亡。在用IndoSN-38或NaproSN-38处理的细胞中发现了亚G1期的细胞周期停滞。总体而言，这些数据表明，NSAID共轭SN-38前药的抗增殖活性是由于促进细胞死亡和阻止细胞周期，这与SN-38的作用相似。
