Establishment of cisplatin-resistant breast cancer cell line and role of FANCF gene in cisplatin resistance
10.3872/j.issn.1007-385x.2018.06.010
- VernacularTitle:顺铂耐药乳腺癌细胞株的建立及F A N C F 基因在耐药中的作用
- Author:
MA Yun
1
;
LI Shumo
2
;
JIANG Aimei
2
;
DONG Jian
1
Author Information
1. The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
2. Department of Breast Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032,Yunnan, China
- Publication Type:Journal Article
- Keywords:
breast cancer;cisplatin (DDP);
MDA-MB-231/DDPcell;
drug resistance;
FANCF gene
- From:
Chinese Journal of Cancer Biotherapy
2018;25(6):607-612
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the expression profile and function of FANCF gene (a key gene in FA/BRCA pathway) in both cisplatin (DDP)-resistant and DDP-sensitive human triple-negative breast cancer cell lines and to analyze its correlation with DDP-resistance in breast cancer. Methods: The DDP-resistant breast cancer MDA-MB-231 cell line (MDA-MB-231/DDP) was established by induction of gradient DDP. The expression of FANCF gene in both sensitive and resistant cell lines was knocked-down by RNAi interference technology and the knockdown efficiency was validated at both RNA and protein level. The cell viability of MDA-MB-231 cells and MDA-MB-231/DDP cells was determined by the CCK8 assay; Flow cytometry was used to examine the cell cycle distribution and apoptosis; the mRNAand protein expressions of FANCF gene were examined by using qRT-PCR and western blotting, respectively. Results: The resistance index of MDA-MB-231/DDP cells was 13.5 after 3-month induction. The mRNA and protein expressions of FANCF were significantly increased in MDA-MB-231/DDP cells (all P<0.01). Cell cycle analysis indicated that the DDP treatment significantly induced G0/G1 arrest and decreased the cell proportion in phase S and G2/M. siRNA-mediated knockdown of FANCF could not only be able to increase sensitivity of MDA-MB-231 to DDP but also promote the cell apoptosis (all P<0.01). Conclusion: FANCF attributes to the occurrence of DDP-resistance through anti-apoptosis effect, which might be served as a potential treatment target for drug-resistant human breast cancer.
- Full text:20180610.pdf