Quercetin Mediates β-Catenin in Pancreatic Cancer Stem-Like Cells.
OBJECTIVE
The aim of this study is to explore how quercetin interacts with pancreatic cancer stem-like cells and the mechanism underlying the effective quercetin-mediated suppression.


METHODS
A model of pancreatic cancer stem-like cells was generated by using a sphere formation culture system. A comparative analysis was performed between the parent cells and pancreatic cancer stem-like cells with a related treatment strategy focusing on cancer stem cell (CSC) properties and drug-resistance-related mechanisms in vitro.


RESULTS
Our data show that pancreatic cancer stem-like cells have greater resistance to gemcitabine and stronger CSC properties compared with the parent cells. In contrast to the pancreatic cancer stem-like cells, overexpression of β-catenin was observed in the parent cells. Quercetin suppressed proliferation, invasion and self-renewal capacity, and CSC surface markers expression, with alterations of β-catenin in pancreatic cancer stem-like cells. The combination of quercetin and gemcitabine can reduce tumor growth and decrease drug resistance in pancreatic cancer.


CONCLUSIONS
β-Catenin plays an important role in maintenance and progression of pancreatic cancer. Targeting β-catenin using quercetin combined with gemcitabine may be a treatment strategy to improve prognosis in patients with pancreatic cancer.
From the *Department of Radiation Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing; †Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou; and ‡State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Caineng
C
Cao
Lixin
L
Sun
Wenxiu
W
Mo
Lichao
L
Sun
Jingwei
J
Luo
Zhihua
Z
Yang
Yuliang
Y
Ran
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D014408:Biomarkers, Tumor; D051176:beta Catenin; D003841:Deoxycytidine; D011794:Quercetin; D000093542:Gemcitabine