Amyloid precursor protein regulates 5-fluorouracil resistance in human hepatocellular carcinoma cells by inhibiting the mitochondrial apoptotic pathway / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
; (12): 234-245, 2020.
Article
in En
| WPRIM
| ID: wpr-1010530
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Amyloid beta-Protein Precursor
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Apoptosis
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Carcinoma, Hepatocellular
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Drug Resistance, Neoplasm
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Proto-Oncogene Proteins c-bcl-2
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Cell Line, Tumor
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Bcl-X Protein
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Fluorouracil
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Liver Neoplasms
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Mitochondria
Limits:
Humans
Language:
En
Journal:
Journal of Zhejiang University. Science. B
Year:
2020
Type:
Article