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Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties

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Abstract

Temozolomide is an alkylating agent which is used in glioblastoma treatment. We aimed to investigate the effects of different concentrations of temozolomide and exposure time on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9 and VEGF. U87MG cells were cultured in different temozolomide concentrations and incubation time and the effects of temozolomide on inducing apoptosis was investigated. The levels of VEGF and CXCR4 expression were measured by RT-PCR and flowcytometry. Moreover, MMP2 and MMP9 activity and expression were assessed by ELISA and zymography. CXCR4 and VEGF expression levels decreased upon applying higher concentration of temozolomide. MMP2 and MMP-9 had lower activity in cells with longer exposure time or higher doses of temozolomide. Temozolomide induces the apoptosis in U87MG glioblastoma cells at therapeutic or higher dose. It is capable of decreasing their expression levels of VEGF and CXCR4.

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Abbreviations

PBT:

Primary brain tumor

CNS:

Central nervous system

GBM:

Glioblastoma

BBB:

Blood brain barrier

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Acknowledgments

This work was performed in partial fulfillment of the requirements for, Pharm. Dr. of Seyedsaber Mirabdaly 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: 90076) for the financial support.

Funding

This work was supported by Research Council of Kermanshah University of Medical Sciences.

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Authors and Affiliations

  1. Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Seyedsaber Mirabdaly

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Daniel Elieh Ali Komi

  3. Department of Immunology, Tabriz University of Medical Sciences, Tabriz, Iran

    Daniel Elieh Ali Komi

  4. Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran

    Yadollah Shakiba & Amir Kiani

  5. Department of Internal Medicine Imam, Reza Hospital Kermanshah University of Medical Sciences, Kermanshah, Iran

    Ali Moini

  6. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Amir Kiani

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  1. Seyedsaber Mirabdaly
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  3. Yadollah Shakiba
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  4. Ali Moini
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Seyedsaber Mirabdaly, Daniel Elieh Ali Komi and Amir Kiani. The first draft of the manuscript was written by Amir Kiani and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Amir Kiani.

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Mirabdaly, S., Elieh Ali Komi, D., Shakiba, Y. et al. Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties. Mol Biol Rep 47, 1187–1197 (2020). https://doi.org/10.1007/s11033-019-05219-2

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