Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/AKT/mTOR axis in human pancreatic cancer cells.
The triggering of gemcitabine (GEM) drug resistance in pancreatic cancer by the receptor for advanced glycation end products (RAGE) has been demonstrated. Hence, finding a safe and effective adjuvant for preventing pancreatic cancer progression is imperative. Quercetin is a flavonoid that is abundant in apples, grapes, red raspberry, and onions and has been reported to inhibit RAGE. This research aimed to investigate the mechanisms of quercetin in regulating cell death and enhancing drug effects through RAGE reduction, especially in GEM-resistant pancreatic cancer cells. Our results showed that silencing RAGE expression by RAGE-specific siRNA transfection significantly increased cell death by apoptosis, autophagy and GEM-induced cytotoxicity by suppressing the PI3K/AKT/mTOR axis in MIA Paca-2 and MIA Paca-2 GEMR cells (GEM-resistant cells). Notably, quercetin showed a dramatic effect similar to RAGE silencing that effectively attenuated RAGE expression to facilitate cell cycle arrest, autophagy, apoptosis, and GEM chemosensitivity in MIA Paca-2 GEMR cells, suggesting that an additional reaction occurred under combined quercetin and GEM treatment. In conclusion, the results demonstrated that the molecular mechanisms of quercetin in regulating apoptosis and autophagy-related pathways and increasing GEM chemosensitivity in pancreatic cancer cells involved inhibition of RAGE expression.
['Lan|Chieh-Yu|CY|', 'Chen|Sheng-Yi|SY|', 'Kuo|Chia-Wen|CW|', 'Lu|Chi-Cheng|CC|', 'Yen|Gow-Chin|GC|']
D000970:Antineoplastic Agents D016923:Cell Death D045744:Cell Line, Tumor D049109:Cell Proliferation D019008:Drug Resistance, Neoplasm D004354:Drug Screening Assays, Antitumor D006801:Humans D010190:Pancreatic Neoplasms D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D011794:Quercetin D000067759:Receptor for Advanced Glycation End Products D058570:TOR Serine-Threonine Kinases
Quercetin RAGE Pancreatic cancer Autophagy Gemcitabine resistance