Down-regulation of Beclin1 inhibits the resistance of ovarian cancer A2780/DDP cells for the cisplatin
10.3872/j.issn.1007-385x.2020.06.004
- VernacularTitle:下调Beclin1抑制卵巢癌A2780/DDP细胞对顺铂的耐药性
- Author:
GUO Yunhong
1
;
TIAN Xiaoyu
1
;
DENG Qiaozi
1
;
ZHANG Kequn
1
Author Information
1. Departmen of Obstetrics and Gynecology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, Henan, China
- Publication Type:Journal Article
- Keywords:
Beclin1;
ovarian cancer;
A2780 cells;
cisplatin;
drug-resistant;
cell autophagy;
apoptosis
- From:
Chinese Journal of Cancer Biotherapy
2020;27(6):615-621
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To investigate the effect of Beclin1 knockdown on cisplatin resistance in ovarian cancer A2780 cells and its related mechanisms. Methods: The mRNA and protein expressions of Beclin1 in A2780 cells and drug resistant A2780/DDP cells were determined by qPCR and Western blotting. After transfection with Beclin1 siRNA, the sensitivity of A2780/DDP cells to cisplatin was detected by MTT assay; Cell clone formation and apoptosis were detected by the Colony formation assay and Flow cytometry assay, respectively; cell autophagy was monitored by monodansylcadaverin (MDC) staining. Furthermore, the protein levels of cell autophagy related proteins, lysosomal associated membrane protein Lamp-2 and Cathepsin B were detected by Western blotting. Results: The mRNA and protein expression levels of Beclin1 in cisplatin-resistant A2780/DDP cells were significantly higher than those in A2780 cells (all P<0.05). The expression of Beclin1 was significantly increased in A2780 cells after treated with cisplatin (P<0.05). Beclin1 knockdown promoted cisplatin induced apoptosis of A2780/DDP cells (P<0.05), inhibited autophagy and cell colony formation (all P<0.05), and increased cell sensitivity to cisplatin (P<0.05). Meanwhile, Western blotting showed that Beclin1 knockdown increased the protein levels of cleaved-caspase 3 and Cathepsin B in A2780/DDP cells, while down-regulated the protein expressions of Atg3, Atg7, LC3Ⅱ/Ⅰand Lamp-2 (all P<0.05). Conclusion: Beclin1 knockdown can improve the sensitivity of A2780/DDP cells to cisplatin, and the mechanism may be related to the inhibition of protective autophagy of cells by regulating the expressions of autophagy related proteins, and the regulation of lysosomes, thus further promoting cisplatin-induced apoptosis of drug-resistant cells.
- Full text:20200604.pdf
