NTNG1 Modulates Cisplatin Resistance in Epithelial Ovarian Cancer Cells via the GAS6/AXL/Akt Pathway
作者全名:"Fang, Shanyu; Luo, Yuanyuan; Zhang, Ying; Wang, Houmei; Liu, Qianfen; Li, Xinya; Yu, Tinghe"
作者地址:"[Fang, Shanyu; Luo, Yuanyuan; Zhang, Ying; Wang, Houmei; Liu, Qianfen; Li, Xinya; Yu, Tinghe] Chongqing Med Univ, Affiliated Hosp 2, Lab Obstet & Gynecol, Chongqing, Peoples R China"
通信作者:"Yu, TH (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Lab Obstet & Gynecol, Chongqing, Peoples R China."
来源:FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
ESI学科分类:MOLECULAR BIOLOGY & GENETICS
WOS号:WOS:000673693300001
JCR分区:Q1
影响因子:5.5
年份:2021
卷号:9
期号:
开始页:
结束页:
文献类型:Article
关键词:NTNG1; cisplatin resistance; ovarian cancer; Axl; DNA repair
摘要:"Cisplatin resistance is a challenge in the treatment of epithelial ovarian cancer. Here, clinical data showed that the level of netrin-G1 (NTNG1) in cisplatin-resistant cancer was higher than that in cisplatin-sensitive cancer (2.2-fold, p = 0.005); patients with a high NTNG1 level in cancer tissues had shorter progression-free survival (11.0 vs. 25.0 months, p = 0.010) and platinum-free interval (5.0 vs. 20.0 months, p = 0.021) compared with patients with a low level. Category- or stage-adjusted analyses demonstrated that the association between the NTNG1 level and prognosis occurred in type II or FIGO III/IV cancer. The basal level of NTNG1 in SKOV3/DDP cells (a cisplatin-resistant subline) was higher than that in SKOV3 cells; therefore, NTNG1 was overexpressed in SKOV3 cells, or silenced in SKOV3/DDP cells. Knocking in NTNG1 reduced the action of cisplatin to decrease cell death and apoptosis of SKOV3 cells, accompanied by upregulation of p-AXL, p-Akt and RAD51; however, opposite effects were observed in SKOV3/DDP cells after knocking down NTNG1. Co-immunoprecipitation demonstrated that NTNG1 bound GAS6/AXL. Silencing NTNG1 enhanced cisplatin effects in vivo, decreasing tumor volume/mass. These data suggested that a high NTNG1 level can result in cisplatin resistance in ovarian cancer cells via the GAS6/AXL/Akt pathway and that NTNG1 may be a useful target to overcome resistance."
基金机构:"Second Affiliated Hospital, Chongqing Medical University [2017-74, CYB20152]"
基金资助正文:"This work was supported by The Second Affiliated Hospital, Chongqing Medical University (2017-74 and CYB20152)."