Effect of inhibiting HSP70 gene expression on proliferation, invasion and migration of cholangiocarcinoma cells and its mechanism
10.3760/cma.j.cn431274-20241019-01575
- VernacularTitle:抑制 HSP70基因表达对胆管癌细胞增殖、侵袭和迁移的影响及其机制
- Author:
Bao ZHANG
1
;
Xiaochen ZENG
1
;
Shengguang SHU
1
Author Information
1. 湖南省第二人民医院普外胸外科，长沙 410007
- Publication Type:Journal Article
- Keywords:
Bile duct neoplasms;
Heat shock protein 70;
Toll-like receptor 4;
MAP kinase signaling system
- From:
Journal of Chinese Physician
2025;27(7):1050-1056
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of inhibiting heat shock protein 70 ( HSP70) gene expression on the proliferation, invasion and migration of cholangiocarcinoma cells and its mechanism. Methods:Tumor tissues and adjacent normal tissue samples from 23 patients with cholangiocarcinoma who underwent surgery in the Hunan Second People′s Hospital from January 2022 to June 2023 were collected. The mRNA and protein expressions of HSP70 in cholangiocarcinoma tissues, human cholangiocarcinoma cells (HuCC-T1), normal bile duct tissues and human intrahepatic biliary epithelial cells (HIBEpiC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. HuCC-T1 cells were cultured in vitro, and a HuCC-T1 cell line with stably knocked down HSP70 gene (HuCC-T1-HSP70-KD group) was obtained by screening after infection with shRNA lentivirus. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the effects of inhibiting HSP70 gene expression on the proliferation, invasion and migration abilities of HuCC-T1 cells. Western blot was used to detect the protein expressions of Toll-like receptor (TLR) 4, phosphorylated extracellular regulated protein kinases 1/2 (p-ERK1/2), ERK1/2, β-catenin, c-myc, Snail and E-cadherin after inhibiting HSP70 gene expression in HuCC-T1 cells. Results:Compared with normal bile duct tissues and HIBEpiC cells, the mRNA and protein expressions of HSP70 in cholangiocarcinoma tissues and HuCC-T1 cells were significantly higher (all P<0.05). After inhibiting HSP70 gene expression in HuCC-T1 cells, the proliferation, invasion and migration abilities of cells in the HuCC-T1-HSP70-KD group were significantly decreased (all P<0.05); the protein expressions of TLR4, p-ERK1/2, β-catenin, c-myc and Snail in the HuCC-T1-HSP70-KD group were significantly decreased, while the protein expression of E-cadherin was significantly increased (all P<0.05). Conclusions:Silencing HSP70 gene expression can significantly inhibit the proliferation, invasion and migration abilities of cholangiocarcinoma cells. The mechanism may be that after the down-regulation of HSP70 gene expression, its activation of downstream TLR4 and MAPK pathways is significantly inhibited, thereby affecting the proliferation, invasion and migration of cholangiocarcinoma cells.
