Migration-prone glioma cells show curcumin resistance associated with enhanced expression of miR-21 and invasion/anti-apoptosis-related proteins
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Wei-Lan Yeh1,*, Hsiao-Yun Lin2,*, Chiung-Yin Huang3, Bor-Ren Huang4,5, Chingju Lin6, Dah-Yuu Lu2,7 and Kuo-Chen Wei3
1 Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua, Taiwan
2 Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan
3 Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
4 School of Medicine, Tzu Chi University, Hualien, Taiwan
5 Department of Neurosurgery, Taichung Tzu Chi General Hospital, Taichung, Taiwan
6 Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan
7 Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan
* These authors have contributed equally to this work
Kuo-Chen Wei, email:
Dah-Yuu Lu, email:
Keywords: migration, glioma, curcumin, miR-21, death receptor
Received: July 08, 2015 Accepted: September 23, 2015 Published: October 12, 2015
In study, the expression patterns and functional differences between an original glioma cell population (U251 and U87) and sublines (U251-P10, U87-P10) that were selected to be migration-prone were investigated. The expressions levels of VEGF and intracellular adhesion molecule-1 (ICAM-1) were increased in the migration-prone sublines as well as in samples from patients with high-grade glioma when compared to those with low-grade glioma. In addition, cells of the migration-prone sublines showed increased expression of the oncogenic microRNA. miR-21, which was also associated with more advanced clinical pathological stages in the patient tissue specimens. Treatment of U251 cells with an miR-21 mimic dramatically enhanced the migratory activity and expression of anti-apoptotic proteins. Furthermore, treatment with curcumin decreased the miR-21 level and anti-apoptotic protein expression, and increased the expression of pro-apoptosis proteins and microtubule-associated protein light chain 3-II (LC3-II) in U251 cells. The migration-prone sublines showed decreased induction of cell death markers in response to curcumin treatment. Finally, U251-P10 cells showed resistance against curcumin treatment. These results suggest that miR-21 is associated with regulation of the migratory ability and survival in human glioma cells. These findings suggest novel mechanisms of malignancy and new potential combinatorial strategies for the management of malignant glioma.
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