4-Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine-resistant pancreatic cancer cells

被引:10
作者
Chen, Ying-Yin [1 ]
Chen, Sheng-Yi [1 ]
Li, Tsung-Ju [2 ]
Lin, Ting-Wei [2 ]
Chen, Chin-Chu [2 ]
Yen, Gow-Chin [1 ]
机构
[1] Natl Chung Hsing Univ, Dept Food Sci & Biotechnol, 145 Xingda Rd, Taichung 40227, Taiwan
[2] Grape King Bio Ltd, Biotech Res Inst, Taoyuan 32542, Taiwan
关键词
4-acetylantroquinonol B; apoptosis; autophagy; gemcitabine; pancreatic cancer; cell invasion; MESENCHYMAL TRANSITION; PROLIFERATION; SENSITIVITY; MECHANISMS; APOPTOSIS; MIGRATION; INVASION;
D O I
10.3892/ol.2022.13248
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gemcitabine (GEM) is a typical chemotherapeutic drug used to treat pancreatic cancer, but GEM resistance develops within weeks after chemotherapy. Hence, the development of a new strategy to overcome drug resistance is urgent. 4-Acetylantroquinonol B (4-AAQB), a ubiquinone derived from Taiwanofungus camphoratus, has hepatoprotective, anti-obesity, and antitumor activities. However, the role of 4-AAQB in enhancing GEM sensitivity is unclear. This study aimed to determine the underlying mechanisms by which 4-AAQB enhances cytotoxicity and GEM sensitivity. Cell viability was dramatically reduced by 4-AAQB (2 and 5 mu M) treatment in the MiaPaCa-2 and GEM-resistant MiaPaCa-2 (MiaPaCa-2(GEMR)) human pancreatic cancer cells. 4-AAQB led to cell cycle arrest, upregulated the levels of reactive oxygen species (ROS), promoted apoptosis, and inhibited autophagy, which subsequently enhanced GEM chemosensitivity by suppressing the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1)-initiated PI3K/Akt/multidrug resistance protein 1 (MDR1) signaling pathway in both cell lines. Vascular endothelial growth factor A (VEGFA) expression, cell migration, and invasion were also inhibited by the 4-AAQB incubation. Overall, this combination treatment strategy might represent a novel approach for GEM-resistant pancreatic cancer.
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页数:13
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