Amyloid precursor protein regulates 5-fluorouracil resistance in human hepatocellular carcinoma cells by inhibiting the mitochondrial apoptotic pathway.
- Author:
Xiao-Long WU
1
;
Ying CHEN
1
;
Wen-Cui KONG
1
;
Zhong-Quan ZHAO
1
Author Information
- Publication Type:Journal Article
- Keywords: Amyloid precursor protein; 5-Fluorouracil resistance; Mitochondrial apoptotic pathway; Hepatocellular carcinoma
- MeSH: Amyloid beta-Protein Precursor/physiology*; Apoptosis/drug effects*; Carcinoma, Hepatocellular/drug therapy*; Cell Line, Tumor; Drug Resistance, Neoplasm; Fluorouracil/pharmacology*; Humans; Liver Neoplasms/drug therapy*; Mitochondria/physiology*; Proto-Oncogene Proteins c-bcl-2/genetics*; bcl-X Protein/genetics*
- From: Journal of Zhejiang University. Science. B 2020;21(3):234-245
- CountryChina
- Language:English
- Abstract: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality globally. It accounts for the majority of primary liver cancer cases. Amyloid precursor protein (APP), a cell membrane protein, plays a vital role in the pathogenesis of Alzheimer's disease, and has been found to be implicated in tumor growth and metastasis. Therefore, to understand the relationship between APP and 5-fluorouracil (5-FU) resistance in liver cancer, Cell Counting Kit-8, apoptosis and cell cycle assays, western blotting, and reverse transcription-quantitative polymerase chain reaction (qPCR) analysis were performed. The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated, as compared with that in Bel7402 cells. Through successful construction of APP-silenced (siAPP) and overexpressed (OE) Bel7402 cell lines, data revealed that the Bel7402-APP751-OE cell line was insensitive, while the Bel7402-siAPP cell line was sensitive to 5-FU in comparison to the matched control group. Furthermore, APP overexpression decreased, while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells. Mechanistically, APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes (B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl)). Taken together, these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU, providing a new perspective for drug resistance.
