scholarly journals IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells

Oncotarget ◽  
2017 ◽  
Vol 8 (24) ◽  
pp. 39154-39166 ◽  
Author(s):  
Xiaolan Zhu ◽  
Huiling Shen ◽  
Xinming Yin ◽  
Lulu Long ◽  
Xiaofang Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Feedback Loop ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cells

scholarly journals A Feedback Loop Between miR-30a/c-5p and DNMT1 Mediates Cisplatin Resistance in Ovarian Cancer Cells

2017 ◽  
Vol 41 (3) ◽  
pp. 973-986 ◽  
Author(s):  
Xi Han ◽  
Shuai Zhen ◽  
Zhongxue Ye ◽  
Jiaojiao Lu ◽  
Lijie Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Feedback Loop ◽  
Cisplatin Resistance ◽  
Expression Patterns ◽  
Family Members ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Aberrant Methylation ◽  
Mesenchymal Transition

Background: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells. Methods: qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR. Results: miR-30a-5p and miR-30c-5p, in contrast to other miR-30 family members, dramatically decreased in cisplatin-resistant CP70 cells due to overexpressed-DNMT1 induced aberrant methylation. miR-30a/c-5p in turn directly inhibited DNMT1 as well as Snail. Forced expression of miR-30a/c-5p or knocking down of DNMT1 and Snail promoted cisplatin susceptibility and partially reversed epithelial-mesenchymal transition (EMT) in CP70 cells, while inhibition of miR-30a/c-5p or ectopic expression of DNMT1 and Snail induced cisplatin resistance and partial EMT in cisplatin-sensitive A2780 cells. Conclusions: A feedback loop between miR-30a/c-5p and DNMT1 is a potent signature for cisplatin-resistance and EMT in ovarian cancer, promising a potential target for improved anti-cancer treatment.

scholarly journals EGFR Blockade Reverses Cisplatin Resistance in Human Epithelial Ovarian Cancer Cells

2020 ◽  
Vol 24 (6) ◽  
pp. 365-373
Author(s):  
Arash Poursheikhani ◽  
Hassan Yousefi ◽  
Javad Tavakoli-bazzaz ◽  
Seyed H. Ghaffari ◽  
◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cells

scholarly journals NTNG1 Modulates Cisplatin Resistance in Epithelial Ovarian Cancer Cells via the GAS6/AXL/Akt Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shanyu Fang ◽  
Yuanyuan Luo ◽  
Ying Zhang ◽  
Houmei Wang ◽  
Qianfen Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Progression Free Survival ◽  
Akt Pathway ◽  
Ovarian Cancer Cells ◽  
Skov3 Cells ◽  
Cancer Tissues

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.

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