Ibuprofen reduces cell proliferation through inhibiting Wnt/ catenin signaling pathway in gastric cancer stem cells

被引:46
作者
Akrami, Hassan [1 ]
Moradi, Behrouz [1 ]
Farahani, Diba Borzabadi [1 ]
Mehdizadeh, Kiumars [1 ]
机构
[1] Razi Univ, Dept Biol, Fac Sci, Kermanshah, Iran
关键词
cancer stem cell (CSC); gastric cancer; nonsteroidal anti-inflammatory drug (NSAID); Wnt signaling pathway; EXPRESSION; TUMORIGENESIS; INTERACTS; TRENDS; GROWTH; P53;
D O I
10.1002/cbin.10959
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nowadays, most studies focused on cancer stem cells (CSCs) through their abilities to cause tumorigenicity, drug resistance, and cancer recurrence. On the other side, nonsteroidal anti-inflammatory drugs (NSAIDs) have been taken into consideration because of cheapness and availability. For the reasons mentioned above, we have studied the effect of ibuprofen as an NSAID on CSCs derived from AGS and MKN-45 gastric cancer cell lines to perform effective cancer therapy. We evaluated cell viability, spheroid body formation, monolayer, and soft agar colony formation to express the anti-cancer effect of ibuprofen on CSCs. Also, real-time RT-PCR data of stemness markers and genes affected on, or downstream of Wnt signaling pathway were evaluated. Our findings suggest that ibuprofen at 1,000M for 48h can reduce cell proliferation, stemness features in CSCs by changing the expression level of CD44, OCT3/4, SOX2, Nanog, and KLF4 as stemness markers. Furthermore, ibuprofen can have an inhibitory role in Wnt signaling pathway by changing the expression level of some genes, including CTNNB1, CTNNBIP1, SMARCD1, PYGO2, SUFU, CASK, and KREMEN1. According to our study, ibuprofen has an anti-proliferative effect on CSCs derived from AGS and MKN-45 cells.
引用
收藏
页码:949 / 958
页数:10
相关论文
共 43 条
[1]   Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell [J].
Akrami, Hassan ;
Aminzadeh, Saman ;
Fallahi, Hossein .
TUMOR BIOLOGY, 2015, 36 (05) :3237-3243
[2]   Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis [J].
Bonelli, P. ;
Tuccillo, F. M. ;
Calemma, R. ;
Pezzetti, F. ;
Borrelli, A. ;
Martinelli, R. ;
De Rosa, A. ;
Esposito, D. ;
Palaia, R. ;
Castello, G. .
PHARMACOGENOMICS JOURNAL, 2011, 11 (06) :412-428
[3]   Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations [J].
Bonelli, Patrizia ;
Tuccillo, Franca M. ;
Federico, Antonella ;
Napolitano, Maria ;
Borrelli, Antonella ;
Melisi, Daniela ;
Rimoli, Maria G. ;
Palaia, Raffaele ;
Arra, Claudio ;
Carinci, Francesco .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2012, 7 :5683-5691
[4]   Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner [J].
Causeret, F. ;
Sumia, I ;
Pierani, A. .
CELL DEATH AND DIFFERENTIATION, 2016, 23 (02) :333-342
[5]   SOX2 inhibits metastasis in gastric cancer [J].
Chen, Yansu ;
Huang, Yefei ;
Zhu, Liwen ;
Chen, Minjuan ;
Huang, Yulin ;
Zhang, Jianbing ;
He, Song ;
Li, Aiping ;
Chen, Rui ;
Zhou, Jianwei .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2016, 142 (06) :1221-1230
[6]  
Chiurillo MA, 2015, WORLD J EXP MED, V5, P84, DOI DOI 10.5493/WJEM.V5.I2.84
[7]   Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype [J].
Ferro, Ana ;
Peleteiro, Barbara ;
Malvezzi, Matteo ;
Bosetti, Cristina ;
Bertuccio, Paola ;
Levi, Fabio ;
Negri, Eva ;
La Vecchia, Carlo ;
Lunet, Nuno .
EUROPEAN JOURNAL OF CANCER, 2014, 50 (07) :1330-1344
[8]   miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45 [J].
Golestaneh, Azadeh Fahim ;
Atashi, Amir ;
Langroudi, Lida ;
Shafiee, Abbas ;
Ghaemi, Nasser ;
Soleimani, Masoud .
CELL BIOCHEMISTRY AND FUNCTION, 2012, 30 (05) :411-418
[9]   Wnt1 and SFRP1 as potential prognostic factors and therapeutic targets in cutaneous squamous cell carcinoma [J].
Halifu, Y. ;
Liang, J. Q. ;
Zeng, X. W. ;
Ding, Y. ;
Zhang, X. Y. ;
Jin, T. B. ;
Yakeya, B. ;
Abudu, D. ;
Zhou, Y. M. ;
Liu, X. M. ;
Hu, F. X. ;
Chai, L. ;
Kang, X. J. .
GENETICS AND MOLECULAR RESEARCH, 2016, 15 (02)
[10]   Sox2 inhibits Wnt-β-catenin signaling and metastatic potency of cisplatin-resistant lung adenocarcinoma cells [J].
He, Jinxi ;
Shi, Juan ;
Zhang, Kangjian ;
Xue, Jing ;
Li, Jing ;
Yang, Jiali ;
Chen, Juan ;
Wei, Jun ;
Ren, Hong ;
Liu, Xiaoming .
MOLECULAR MEDICINE REPORTS, 2017, 15 (04) :1693-1701