Migration-prone glioma cells show curcumin resistance associated with enhanced expression of miR-21 and invasion/anti-apoptosis-related proteins.

Wei-Lan Yeh,Chingju Lin,Kuo-Chen Wei,Bor-Ren Huang,Dah-Yuu Lu,Hsiao-Yun Lin,Chiung-Yin Huang

doi:10.18632/oncotarget.6092

Abstract

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.

Highlights

Human tumors tend to contain a variety of cellular subpopulations with different characteristics and behaviors with respect to cellular activities involved in gene expression, morphology changes, metabolism, proliferation, drug responsiveness, and motility [1-3]; this property is geneally referred to as intratumoral heterogeneity
The migration-prone subline cells were selected from two different glioma cell lines, U251 and U87, and designated as U251-P10 and U87-P10, respectively
Our data indicated that upregulation of VEGF and intracellular adhesion molecule-1 (ICAM-1) is associated with the pathological features of gliomas migration

Summary

Introduction

Human tumors tend to contain a variety of cellular subpopulations with different characteristics and behaviors with respect to cellular activities involved in gene expression, morphology changes, metabolism, proliferation, drug responsiveness, and motility [1-3]; this property is geneally referred to as intratumoral heterogeneity. Human tumors tend to contain a variety of cellular subpopulations with different characteristics and behaviors with respect to cellular activities involved in gene expression, morphology changes, metabolism, proliferation, drug responsiveness, and motility [1-. Most human cancers contain distinct cellular subpopulations with different genetic alterations and behaviors [6]. The intratumoral heterogeneity of malignant glioma has been reported to be responsible for the high frequency of therapeutic failure [12, 13]. These findings indicate that it is important to understand the heterogeneity of glioma in order to develop more effective treatment strategies

Methods

Results

Conclusion