Department of Premedical Course, Chosun University School of Medicine, Gwangju, Republic of Korea.
Department of Medicine, Gradulat School of Chosun University, Gwangju, Republic of Korea.
Anticancer Res. 2019 Nov;39(11):6097-6105. doi: 10.21873/anticanres.13817.
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most common in the world and its prevalence is rapidly increasing. Jagged-1-activated Notch signaling by apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) promotes CRC, and high expression of Jagged-1 is associated with poor prognosis. However, its clinical implication is unknown. The aim of this study was to investigate the clinical role of Jagged-1-activated Notch signaling by APEX1.
The 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the anti-cancer efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. Tissue from CRC patients was analyzed to assess the clinical specificity of Jagged-1 activated by APEX1.
The half-maximal inhibitory concentration (IC) in cells co-expressing APEX1 and Jagged-1 cells was higher than that in cells expressing only APEX1. These results indicated that the simultaneous expression of APEX1 and Jagged-1 might be associated with chemoresistance toward 5-FU, oxaliplatin, and irinotecan. Analysis of tissue from CRC patients revealed that high expression of Jagged-1 was associated with a statistically significantly low response to chemotherapy.
Overexpression of Jagged-1 by APEX1 might serve as a predictor of response to chemotherapy and of poor prognosis, and moreover may be a therapeutic target for chemotherapy of advanced CRC.
背景/目的：结直肠癌（CRC）是世界上最常见的癌症之一，其发病率正在迅速上升。APEX1 激活的锯齿状 1 激活的 Notch 信号促进 CRC 的发生，而锯齿状 1 的高表达与预后不良相关。然而，其临床意义尚不清楚。本研究旨在探讨 APEX1 激活的 Notch 信号在 CRC 中的临床作用。
使用 5-（二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定法评估氟尿嘧啶（5-FU）、奥沙利铂和伊立替康的抗癌疗效。分析 CRC 患者的组织样本，以评估 APEX1 激活的锯齿状 1 的临床特异性。
共表达 APEX1 和 Jagged-1 的细胞的半最大抑制浓度（IC）高于仅表达 APEX1 的细胞。这些结果表明 APEX1 和 Jagged-1 的同时表达可能与对 5-FU、奥沙利铂和伊立替康的化疗耐药性有关。对 CRC 患者组织的分析表明，Jagged-1 的高表达与化疗反应率显著降低相关。
APEX1 过表达 Jagged-1 可能是化疗反应和预后不良的预测因子，并且可能是晚期 CRC 化疗的治疗靶点。
