Molecular mechanism of apoptosis of breast cancer SKBR-3 cells induced by cryptanshinone via G protein coupled estrogen receptor( GPER) mediated pathway.
10.19540/j.cnki.cjcmm.20190527.401
- Author:
Dan-Ning SHI
1
;
Li-Xia CUI
1
;
Pi-Wen ZHAO
1
;
Li-Ping SUN
1
;
Meng CHEN
2
;
Jian-Zhao NIU
2
Author Information
1. School of Life Sciences,Beijing University of Chinese Medicine Beijing 100029,China.
2. School of Traditional Chinese Medicine,Beijing University of Chinese Medicine Beijing 100029,China.
- Publication Type:Journal Article
- Keywords:
GPER;
PI3K/AKT;
SKBR-3;
breast cancer;
cell apoptosis;
cryptotanshinone;
phytoestrogen
- MeSH:
Apoptosis;
Breast Neoplasms;
Drugs, Chinese Herbal;
Humans;
Proto-Oncogene Proteins c-akt;
Receptors, Estrogen;
Receptors, G-Protein-Coupled;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2019;44(22):4905-4911
- CountryChina
- Language:Chinese
-
Abstract:
The study aimed to illuminate the role of G protein coupled estrogen receptor( GPER) and its mediated PI3 K/AKT signaling pathway in cryptotanshinone( CPT) induced apoptosis of breast cancer SKBR-3 cells,which is GPER positive and ER negative.The apoptosis rate of SKBR-3 cells was tested by Annexin V-FITC/PI staining and apoptosis effector caspase-3 was determined by Western blot. The key proteins in PI3 K/AKT signaling pathway mediated by GPER were detected by Western blot and immunofluorescence technique. Meanwhile,the agonist G1 and antagonist G15 of GPER and antagonist LY294002 of PI3 K were employed in the test to further clarify the effect of GPER and PI3 K/AKT pathway. The results indicated that the apoptosis rate was increased from 4. 7% to46. 1% and 69. 0% after treatment with 0,5,10 μmol·L~(-1) CPT for 48 h( P<0. 01). The expression of PI3 K,AKT and p-AKT were inhibited( P<0. 05 or P<0. 01),while caspase-3 level increased obviously after treatment with CPT( P<0. 01). Importantly,inhibitory effect of PI3 K/AKT signaling pathway by CPT was further enhanced by G1 and attenuated by G15. LY294002 also induced a further inhibition of expression of AKT and p-AKT. The mean fluorescence intensity of AKT and p-AKT could be decreased by CPT. Furthermore,CPT could downregulate GPER expression in SKBR-3 cells( P<0. 01),which could be inhibited by G1 and enhanced by G15.In conclusion,CPT could induce the apoptosis of ER negative and GPER positive breast cancer SKBR-3 cells and the molecular mechanism is related to its regulatory effect of GPER and its mediated PI3 K/AKT signaling pathway.
