Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2727
Revised: March 14, 2024
Accepted: April 23, 2024
Published online: June 15, 2024
Processing time: 165 Days and 17.7 Hours
Previous studies have shown that the Shi-pi-xiao-ji (SPXJ) herbal decoction for
To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.
HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice. The apoptotic rate and proliferative, invasive, and migratory abilities of control and SPXJ-treated HCC cells were compared. Atomic force microscopy was used to determine the cell surface morphology and the Young’s modulus values of the control and SPXJ-treated HCC cells. Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit. ACAT1 protein levels were estimated using western blotting.
Compared with the vehicle group, SPXJ serum considerably reduced proliferation of HCC cells, increased stiffness and apoptosis of HCC cells, inhibited migration and invasion of HCC cells, decreased plasma membrane cholesterol levels, and upregulated ACAT1 protein levels. However, treatment of HCC cells with the water-soluble cholesterol promoted proliferation, migration, and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels, but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control.
SPXJ formula inhibited proliferation, invasion, and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.
Core Tip: Cellular stiffness is a key feature of cellular biomechanics and is determined by cholesterol levels in the plasma membrane. Traditional Chinese medicine (TCM) has demonstrated good anti-tumor effects, but underlying mechanisms are not well characterized. Herein, we investigated the effects of the Shi-pi-xiao-ji (SPXJ) herbal formula on the stiffness of hepatocellular carcinoma (HCC) cells. The SPXJ formula altered the stiffness of HCC cells by decreasing plasma membrane cholesterol levels through upregulation of acetyl-coA acetyltransferase 1. Subsequently, this inhibited the invasion and metastasis of HCC cells. Our study provides a scientific basis for the clinical use of TCM preparations in the treatment of HCC.