FFJ-5 inhibits growth of MCF7 cells and reverses drug resistance of MCF7/DOX cells via down-regulation of PKM2
10.3969/j.issn.1001-1978.2015.05.025
- VernacularTitle:FFJ-5下调PKM2抑制MCF7生长及逆转MCF7／DO X细胞耐药性的研究
- Author:
Tianxiao WANG
;
Xiaoli WEI
;
Dengyun LI
- Publication Type:Journal Article
- Keywords:
FFJ-5;
PKM2;
EGFR;
Akt;
cell apopto-sis;
drug resistant cells;
cell signal pathway
- From:
Chinese Pharmacological Bulletin
2015;(5):721-725,726
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the roles of FFJ-5 in human breast cancer MCF7 cells and drug-resistant MCF7/DOX cells and to explore its mechanisms. Methods MTT assay was used to detect the effect of FFJ-5 on MCF7 and MCF7/DOX cell proliferation and sensitivity of doxorubicin in MCF7/DOX cells.West-ern blot was used to investigate the effect of FFJ-5 on expression of EGFR,p-EGFR,Akt,p-Akt,PKM2, cleaved caspase-3,cleaved PARP and P-gp.DNA lad-der analysis was performed to determine the effect of FFJ-5 on genomic DNA.RT-PCR was performed to de-tect the influence of FFJ-5 on multidrug resistance gene MDR1 mRNA levels.Results The results showed that FFJ-5 inhibited the growth of MCF7 ,inhibited the expression and activity of EGFR and Akt,and conse-quently reduced the expression of PKM2 in MCF7 cells;FFJ-5 activated caspase-3 and induced genomic DNA fragmentation;FFJ-5 also inhibited the growth of MCF7/DOX cells and enhanced the anti-tumor activity of doxorubicin in MCF7/DOX cells.Conclusion The results suggest that FFJ-5 could inhibit MCF7 cell growth and induce MCF7 cell apoptosis through inhibi-tion of EGFR-Akt-PKM2 pathway and activation of ap-optosis-related factors caspase-3 , meanwhile FFJ-5 could also reverse the resistance of MCF7/DOX.
