顺铂
卵巢癌
癌症研究
细胞凋亡
细胞周期蛋白D1
细胞周期
癌症
化学
小RNA
流式细胞术
生物
癌细胞
细胞培养
医学
生存素
基因敲除
下调和上调
基因沉默
MTT法
活力测定
细胞
作者
Y Zuo,W Zheng,Johnson J. Liu,Qunwei Tang,S S Wang,X S Yang
出处
期刊:Neoplasma
[AEPress, s.r.o.]
日期:2020-01-01
卷期号:67 (1): 93-101
被引量:30
标识
DOI:10.4149/neo_2019_190202n106
摘要
Ovarian cancer is the most lethal gynecologic malignancy in women with an increasing number of cases worldwide. Chemoresistance is the main obstacle for ovarian cancer treatment during clinical therapy. Previous studies found that programmed cell death 1 ligand 1 (PD-L1) was associated with chemoresistance of cancer. However, there were little reports about the function of PD-L1 involved in chemoresistance of ovarian cancer. In our study, cisplatin (DDP)-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. We found that the expression of PD-L1 was increased and miR-34a-5p was decreased in DDP-resistant cells. PD-L1 silencing inhibited chemoresistance of DDP-resistant ovarian cancer cells to DDP, as evidenced by decreased proliferation, G1-phase cell cycle arrest and increased apoptosis. Western blot assay showed that in the presence of DDP, PD-L1 silencing decreased multidrug resistance protein 1 and Cyclin D1 protein levels, whereas increased cleaved-caspase-3 and cleaved-PARP protein levels in these cells. Moreover, we demonstrated that miR-34a-5p negatively regulated the expression of PD-L1 by targeting its 3'-untranslated region. The effects of miR-34a-5p mimic on DDP-treated SKOV3/DDP cells were reversed by the overexpression of PD-L1. Moreover, the tumorigenicity of DDP-resistant ovarian cancer cells in nude mice treated with DDP was attenuated by miR-34a-5p in vivo. The combined data indicate that miR-34a-5p/PD-L1 axis regulates DDP chemoresistance of ovarian cancer cells, providing a deeper insight into the treatment for ovarian cancer.
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