Department of Premedical Course, Chosun University School of Medicine, Gwangju, Republic of Korea.
Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju, Republic of Korea.
Anticancer Res. 2020 Apr;40(4):1897-1904. doi: 10.21873/anticanres.14144.
BACKGROUND/AIM: We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells.
We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells. Moreover, gastric tumor samples from 9 patients, divided in 2 groups according to chemotherapy response, were examined by immunocytochemical (IHC) staining, and protein expression levels were scored.
Following APEX1 knockdown, the MTT assay revealed that the IC of cisplatin and 5-FU in AGS cells was decreased approximately 7% and 15%, respectively, however, their decrease in chemoresistant KATO-III cells was decreased by approximately 21% and 67% for cisplatin and 5-FU, respectively. The tumor volume of KATO-III/sicontrol mice treated with cisplatin and 5-FU was affected less, compared with KATO-III/siAPEX1 mice treated with cisplatin and 5-FU. Also, the expression levels of APEX1, Jagged-1 and CD133, assayed by IHC staining, were higher in the chemorefractory group than in the chemoresponsive group.
Jagged-1-activated signaling by APEX1 plays a role in advanced gastric cancer.
背景/目的：我们研究了分子靶点 APEX1 和 Jagged-1 以及 Apex1-Jagged-1 级联在胃癌细胞中的临床作用。
我们使用了 6 个人类胃癌细胞系（SNU-1、SNU-5、SNU-16、NCI-N87、KATO-III 和 AGS），并通过 MTT 测定和免疫印迹法证明了 APEX1 和 Jagged-1 的化学敏感性。通过 KATO-III 细胞注射的异种移植模型，检测顺铂和 5-FU 治疗后的肿瘤生长情况。此外，我们通过免疫细胞化学（ICC）染色检查了 9 名患者的胃癌肿瘤样本，根据化疗反应将其分为 2 组，并对蛋白表达水平进行了评分。
在 APEX1 敲低后，MTT 测定显示 AGS 细胞中顺铂和 5-FU 的 IC 分别降低了约 7%和 15%，然而，在耐药性 KATO-III 细胞中，其降低分别为约 21%和 67%。与接受顺铂和 5-FU 治疗的 KATO-III/siAPEX1 小鼠相比，接受顺铂和 5-FU 治疗的 KATO-III/sicontrol 小鼠的肿瘤体积受影响较小。此外，通过 ICC 染色检测到，在化疗耐药组中，APEX1、Jagged-1 和 CD133 的表达水平高于化疗敏感组。
APEX1 激活的 Jagged-1 信号在晚期胃癌中起作用。
