Shi-pi-xiao-ji formula suppresses hepatocellular carcinoma by reducing cellular stiffness through upregulation of acetyl-coA acetyltransferase 1  

作　　者：Hui-Ying Jian Zi-Cheng Liang Huan Wen Zhen Zhang Pu-Hua Zeng 

机构地区：[1]Graduate School,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [2]Hunan Provincial Hospital of Integrated Traditional Chinese and Western,Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine,Hunan Academy of Chinese Medicine,Changsha 410006,Hunan Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第6期2727-2741,共15页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by the National Natural Science Foundation of China,No.82074425;Hunan Science and Technology Planning Project,No.2016SK2051 and No.2023SK2057;the Hunan Provincial Administration of Traditional Chinese Medicine Research Project,No.B2023089.

摘　　要：BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1(ACAT1)-regulated cellular stiffness.Through a series of experiments,we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1,lowering the level of cholesterol in the cell membrane,and altering the cellular stiffness,which provides a new idea for the research of traditional Chinese medicine against HCC.AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.METHODS 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.RESULTS 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.CONCLUSION SPXJ formula inhibited proliferation,invasion,and migration of HCC cells by decreasing plasma membrane cho

关 键 词：Shi-pi-xiao-ji formula Hepatocellular carcinoma Cellular stiffness Plasma membrane cholesterol level AcetylcoA acetyltransferase 1 

分 类 号：R735.7[医药卫生—肿瘤] R459.3[医药卫生—临床医学]