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

被引：21

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

页码：1664 / 1677

页数：14

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