[Mechanism of the inhibitory effects of thalidomide on expressions of VEGF and bFGF].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
; 38(2): 169-174, 2022 Mar.
Article
em Zh
| MEDLINE
| ID: mdl-36031577
ABSTRACT
Objective:
To investigate the inhibitory effects of thalidomide on the expressions of VEGF and bFGF in human lung adenocarcinoma A549 cells and human hepatocellular carcinomas HepG2 cells mediated by cereblon (CRBN).Methods:
shRNA technology was used to construct the A549 cell line (A549CRBN) and HepG2 cell line (HepG2CRBN) with stable knockdown of CRBN, which was verified by real-time PCR and Western blot. A549 cells were divided into negative control group (A549luciferase) and CRBN down-regulation group (A549CRBN); HepG2 cells were divided into negative control group (HepG2luciferase) and CRBN down-regulation group (HepG2CRBN). The above cells were seeded into 6-well plates at 3×105 cells/well, and cultured in a 37â, 5% CO2 incubator for 24 h. Then, 1 ml medium containing 100 µmol/L thalidomide (thalidomide group) and 1 ml medium containing 1 DMSO (control group) were added respectively, and the culture was continued for 24 hours before subsequent experiments. Each group was designed with three replicate wells. The effect of thalidomide on the activity of A549 cell line was detected by MTS assay. Real-time PCR was performed to detect mRNA expression levels of VEGF, bFGF and c-jun. ELISA assay was performed to detect protein expressions of VEGF and bFGF.Results:
Compared with the control group, thalidomide at the concentrations of 1, 10, 50 and 100 µmol/L had no significant effects on the proliferation of A549 and HepG2 cells (Pï¼0.05). VEGF and bFGF levels in the A549CRBN or HepG2luciferase groups were significantly lower than those in the A549CRBN or HepG2CRBN groups (Pï¼0.05). Compared with the control group of the A549luciferase or HepG2luciferase, thalidomide inhibited the expressions of VEGF and bFGF in A549luciferase and HepG2luciferase cells (Pï¼ 0.05), but did not inhibit the expressions of VEGF and bFGF in A549CRBN and HepG2CRBN cells. Compared with the control group of the HepG2luciferase, thalidomide inhibited c-Jun expression in HepG2luciferase cells (Pï¼0.01), but did not significantly inhibit c-Jun expression in HepG2CRBN cells.Conclusion:
The inhibitory effects of thalidomide on VEGF and bFGF expressions may be mediated by CRBN in A549 and HepG2 cells, and c-Jun may be one of the key transcription factors responsible for this inhibition.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Talidomida
/
Fator A de Crescimento do Endotélio Vascular
Limite:
Humans
Idioma:
Zh
Ano de publicação:
2022
Tipo de documento:
Article