Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal CancerWang H.a,b,c · Liu B.a · Wang J.a,d · Li J.e · Gong Y.f · Li S.a · Wang C.a · Cui B.a · Xue X.a · Yang M.a · Fan W.a · Kang Z.g · Kamran M.a · Xu J.a · Tian P.h · Luo Y.a · Hou Z.a · Dong L.a · Ren Y.h · Li M.f · Wen Q.e · Cheng W.a · Xu L.f · Wang L.h · Liu Q.a,b
aInstitute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China
bState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China
cDepartment of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China
dDepartment of Oncology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, China
eDepartment of Anesthesia, The First Affiliated Hospital, Dalian Medical University, Dalian, China
fDepartment of Oncology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China
gDepartment of Hematology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China
hDepartment of Oncology, The First Affiliated Hospital, Dalian Medical University, Dalian, China
Q Liu, L Wang, LZ Xu and W Cheng
Institute Cancer Stem Cell, Dalian Medical University, Dept Oncol, The First Affiliated Hospital,
Dalian Medical University, Dept Oncol, The Second Affiliated Hospital,
Dalian Medical University, Institute Cancer Stem Cell, Dalian Medical University (China);
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Background/Aims: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.
© 2017 The Author(s). Published by S. Karger AG, Basel
WHO: World Cancer Report 2014, 2014.
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