|Table of Contents|

Effects and mechanism of dexamethasone on proliferation,apoptosis,migration and invasion of PC-3 cells in prostate cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 09
Page:
1607-1614
Research Field:
Publishing date:

Info

Title:
Effects and mechanism of dexamethasone on proliferation,apoptosis,migration and invasion of PC-3 cells in prostate cancer
Author(s):
SU Ruizhen; ZHENG Sichao
Department of Pharmacy,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangdong Guangzhou 510799,China.
Keywords:
dexamethasone; ERK/AKT signaling pathway; prostate cancer; proliferation; apoptosis; migration; invasion
PACS:
R737.25
DOI:
10.3969/j.issn.1672-4992.2024.09.006
Abstract:
Objective:To investigate the effects of dexamethasone(DXMS) on the proliferation,apoptosis,migration and invasion of PC-3 cells in prostate cancer(PCa) cells by inhibiting the extracellular signal-regulated kinase(ERK)/protein kinase B(AKT) signaling pathway.Methods:The PCa cell line PC-3 was cultured in vitro.The cells were divided into control group(dimethyl sulfoxide),DXMS low-dose group(0.01 μmol/L DXMS),DXMS medium-dose group(0.1 μmol/L DXMS),and DXMS high-dose group(1 μmol/L DXMS) and DXMS high-dose+TPA group(1 μmol/L DXMS and 50 μmol/L ERK/AKT signaling pathway activator TPA).The expression of glucocorticoid receptor(GR) was detected by qRT-PCR.Cell viability was detected by CCK-8 assay.Apoptosis was detected by flow cytometry.Cell migration and invasion were detected by Transwell.The expression of GR,apoptosis(pro-caspase-3,cleaved-caspase-3,pro-caspase-9,cleaved-caspase-9,Bcl-2,Bax),metastasis(Vimentin,N-cadherin,E-cadherin),ERK,and AKT proteins were detected by Western blot.PC-3 cell xenograft nude mice were established.DXMS was injected intraperitoneally when the tumor diameter reached 0.5~0.6 cm.A total of 4 groups were set up:control group,DXMS low-dose group(1 mg/kg),DXMS medium-dose group(5 mg/kg),and DXMS high-dose group(25 mg/kg).After 28 days of administration,the tumor volume and weight were measured.Apoptosis was observed by TUNEL staining,and the expression of ERK and AKT proteins was detected by Western blot.Results:With the increase of DXMS dose,the viability,migration rate and invasion rate of PC-3 cells decreased gradually,the level of GR mRNA and protein,apoptosis rate gradually increased,the expression of cleaved caspase-3,cleaved caspase-9,Bax,E-cadherin gradually increased,the expression of Bcl-2,Vimentin and N-cadherin gradually decreased in a significant dose-dependent manner(P＜0.05).After TPA treatment,the phosphorylation levels of ERK and AKT were significantly increased,which could significantly reverse the inhibitory effects of DXMS on proliferation,migration and invasion of PC-3 cells(P＜0.05).The in vivo experiment results showed that DXMS significantly inhibited the growth of PC-3 xenograft tumor,promoted the apoptosis of tumor tissues,and inhibited the phosphorylation of ERK and AKT(P＜0.05).Conclusion:DXMS may accelerate the apoptosis of PC-3 cells and hinder cell proliferation,migration and invasion by inhibiting ERK/AKT signaling pathway.

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Last Update: 2024-03-29