Synergistic Effect of Gefitinib and Temozolomide on U87MG Glioblastoma Angiogenesis

Abstract

One of the most common and deadly brain tumors is Glioblastoma multiforme (GBM). Due to recent advances in angiogenesis and its related key factors, this process as a hallmark in glioblastoma has attracted more consideration from the research community. Temozolomide (TMZ) as the first-line treatment used to treat GBM but, resistance to TMZ limits its effectiveness and the need for better treatments is still felt. Therefore, we aimed to examine the Synergistic effects of Gefitinib (GFI) in combination with Temozolomide on VEGF and MMPs in glioma cell line (U87MG). Our results displayed that GFI could induce cytotoxic effects in U87MG with IC50 values of 11 μM. U87MG cells produced large amounts of VEGF without any stimuli, and the results showed that GFI in combination with TMZ caused a significant decrease in VEGF production in these cells. In this study, we demonstrated that after treating with TMZ and GFI, there was more decrease in the levels of MMP 2 and 9 secretions in cells than treatment with GFI and TMZ doses alone. This study indicates synergistic effects of GFI plus TMZ against glioma are mediated by the potentiated anti-angiogenesis. Therefore, it can be considered as a promising plan for future studies.

Acknowledgments

The information provided in this article was obtained from the Pharm D. thesis of Dr. Maryam Hossienpour in the faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant Number: 96110) for the financial support.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Authors’ Contributions

Afshin Karami and Amir Kiani contributed to the study conception and design. M. Hossienpour contributed to material preparation and collection of data. Data analysis was performed by A. Karami and E. Mohammadi Noori. The first draft of the manuscript was written by A. Kiani and A. Karami. M. Rahpyma, Kh. Najafi contributed to critically revised manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This work was supported by Research Council of Kermanshah University of Medical Sciences (Grant Number: 96110).