Lucidone inhibits autophagy and MDR1 via HMGB1/RAGE/PI3K/Akt signaling pathway in pancreatic cancer cells

被引：22
作者：
Chen, Sheng-Yi [1 ]
Hsu, Yi-Hao [1 ]
Wang, Sheng-Yang [2 ]
Chen, Ying-Yin [1 ]
Hong, Cheng-Jie [1 ]
Yen, Gow-Chin [1 ]
机构：
[1] Natl Chung Hsing Univ, Dept Food Sci & Biotechnol, 145 Xingda Rd, Taichung 40227, Taiwan
[2] Natl Chung Hsing Univ, Dept Forestry, Taichung, Taiwan
来源：
PHYTOTHERAPY RESEARCH | 2022年 / 36卷 / 04期
关键词：
autophagy; gemcitabine; lucidone; MDR1; pancreatic ductal adenocarcinoma; NF-KAPPA-B; PROMOTES CHEMORESISTANCE; UP-REGULATION; HMGB1; RESISTANCE; GEMCITABINE; EXPRESSION; APOPTOSIS; PI3K/AKT; RECEPTOR;
D O I：
10.1002/ptr.7385
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Gemcitabine (GEM) drug resistance remains a difficult challenge in pancreatic ductal adenocarcinoma (PDAC) treatment. Therefore, identifying a safe and effective treatment strategy for PDAC is urgent. Lucidone is a natural compound extracted from the fruits of Lindera erythrocarpa Makino. However, the role of lucidone in PDAC inhibition remains unclear. In addition, high-mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) are involved in multidrug resistance protein 1 (MDR1) regulation and GEM resistance. Thus, this study aimed to explore the function of lucidone in tumor cytotoxicity and chemosensitivity through the suppression of RAGE-initiated signaling in PDAC cells. The data showed that lucidone significantly promoted apoptotic cell death and inhibited the expression of autophagic proteins (Atg5, Beclin-1, LC3-II, and Vps34) and MDR1 by inhibiting the HMGB1/RAGE/PI3K/Akt axis in both MIA Paca-2 cells and MIA Paca-2(GEMR) cells (GEM-resistant cells). Notably, convincing data were also obtained in experiments involving RAGE-specific siRNA transfection. In addition, remarkable cell proliferation was observed after treatment with lucidone combined with GEM, particularly in MIA Paca-2(GEMR) cells, indicating that lucidone treatment enhanced chemosensitivity. Collectively, this study provided the underlying mechanism by which lucidone treatment inhibited HMGB1/RAGE-initiated PI3K/Akt/MDR1 signaling and consequently enhanced chemosensitivity in PDAC.
引用
收藏
页码：1664 / 1677
页数：14
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