Department of Surgical Oncology, Johns Hopkins University, Baltimore, MD, United States of America.
Department of Oncology, Johns Hopkins University, Baltimore, MD, United States of America.
PLoS One. 2018 Jun 21;13(6):e0199130. doi: 10.1371/journal.pone.0199130. eCollection 2018.
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a 'rest period'. Sensitization with guadecitabine improved response to the chemotherapeutic agent-Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.
胰腺导管腺癌 (PDAC) 预计将成为 2030 年癌症死亡率的第二大主要原因。PDAC 仍然对大多数系统化疗具有抗药性。在本文中，我们探讨了表观遗传敏化是否可以提高 PDAC 的化疗反应。用一系列浓度的表观遗传调节剂 5-氮杂胞苷 (Aza) 和 SGI-110 对多个 PDAC 细胞系进行了测试。Guadecitabine 有效抑制 DNA 甲基转移酶 1 (DNMT1) 的表达，并在纳摩尔浓度下降低细胞活力。我们还报告说，Guadecitabine 在延迟期或我们称为“休息期”后具有更高的疗效。Guadecitabine 的敏化作用提高了对化疗药物伊立替康的反应，表现为细胞活力降低，并伴有半胱天冬酶活性增加。需要进一步的研究来了解其作用机制。
