Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effects of mTOR inhibitor, everolimus, on proliferation, autophagy and temozolomide sensitivity of glioma cells

Wei Dong¹, Jialiang Wang² , Haipeng Liu², Shuo Sun², Yanbin Wang²

¹Physical Examination Center; ²Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding City, Hebei Province, Baoding, PR China.

For correspondence:- Jialiang Wang Email: n6044u@163.com

Accepted: 27 December 2019 Published: 31 January 2020

Citation: Dong W, Wang J, Liu H, Sun S, Wang Y. Effects of mTOR inhibitor, everolimus, on proliferation, autophagy and temozolomide sensitivity of glioma cells. Trop J Pharm Res 2020; 19(1):77-82 doi: 10.4314/tjpr.v19i1.12

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To study the effect of the mTOR inhibitor, everolimus, on glioma cell proliferation, autophagy, and drug sensitivity to temozolomide (TMZ).

Methods: Human glioma cell lines were cultured in vitro, and the effects of different concentrations of everolimus on the proliferation of brain glial cells were determined using CCK-8 method. The effect of different concentrations of everolimus on brain glial cell levels of autophagy protein were assayed by western blot method.

Results: The results of CCK-8 analysis showed that everolimus inhibited the proliferation of glial cells in a time- and concentration-dependent manner. Western blot results showed that the expression levels of autophagy proteins, LC3-II and LC3-II/I, were gradually and concentration-dependently up-regulated, while p62 protein level was gradually decreased concentration-dependently, when compared with blank control (p < 0.05). Treatment with different concentrations of TMZ alone, and in combination with everolimus for 48 h inhibited the proliferation of brain glial cells in a concentration-dependent manner, but the inhibition due to TMZ-everolimus combination was significantly higher than that of TMZ single treatment (p < 0.05). After 48 h, the expression level of Beclin-1 increased with the ratio of LC3-II/LC-I in TMZ-everolimus group, while the expression level of p62 decreased, when compared with TMZ alone, or control (p < 0.05).

Conclusion: Everolimus significantly inhibits the proliferation of glioma cells and promotes the occurrence of autophagy. Combined use of TMZ and everolimus significantly enhances the sensitivity of TMZ to glioma cells, inhibits cell proliferation, and promotes autophagy better than TMZ alone.

Keywords: mTOR inhibitor, Everolimus, Glioma cells, Proliferation, Autophagy