Wu Zhengchun, Liu Ziru, Sun Yi, Yuan Yuan, Zou Qiong, Wen Yun, Luo Jia, Liu Rushi
Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan410013, China.
Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan410011, China.
J Cancer. 2023 May 15;14(8):1443-1457. doi: 10.7150/jca.83356. eCollection 2023.
Although APEX1 is associated with the tumorigenesis and progression of some human cancer types, the function of APEX1 in gallbladder cancer (GBC) is unclear. In this study, we found that APEX1 expression is up-regulated in GBC tissues, and APEX1 positive expression is related to aggressive clinicopathological features and poor prognosis of GBC. APEX1 was an independent risk factor of GBC prognosis, and presented some pathological diagnostic significance in GBC. Furthermore, APEX1 was overexpressed in CD133 GBC-SD cells in comparison with GBC-SD cells. APEX1 knockdown increased the sensitivity of CD133 GBC-SD cells to 5-Fluorouracil via facilitating cell necrosis and apoptosis. APEX1 knockdown in CD133 GBC-SD cells dramatically inhibited cell proliferation, migration, and invasion, and promoted cell apoptosis . APEX1 knockdown in CD133 GBC-SD cells accelerated tumor growth in the xenograft models. Mechanistically, APEX1 affected these malignant properties via upregulating Jagged1 in CD133 GBC-SD cells. Thus, APEX1 is a promising prognostic biomarker, and a potential therapeutic target for GBC.
尽管APEX1与某些人类癌症类型的肿瘤发生和进展相关，但APEX1在胆囊癌（GBC）中的功能尚不清楚。在本研究中，我们发现APEX1在GBC组织中表达上调，且APEX1阳性表达与GBC侵袭性临床病理特征及预后不良相关。APEX1是GBC预后的独立危险因素，在GBC中具有一定的病理诊断意义。此外，与GBC-SD细胞相比，APEX1在CD133 GBC-SD细胞中过表达。敲低APEX1通过促进细胞坏死和凋亡增加了CD133 GBC-SD细胞对5-氟尿嘧啶的敏感性。敲低CD133 GBC-SD细胞中的APEX1可显著抑制细胞增殖、迁移和侵袭，并促进细胞凋亡。敲低CD133 GBC-SD细胞中的APEX1可加速异种移植模型中的肿瘤生长。机制上，APEX1通过上调CD133 GBC-SD细胞中的Jagged1影响这些恶性特性。因此，APEX1是一种有前景的预后生物标志物，也是GBC的潜在治疗靶点。
