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DHA Abolishes the Detrimental Effect of Docetaxel on Downregulation of the MICA via Decreasing the Expression Level of MicroRNA-20a in Gastric Cancer

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Abstract

Background

MHC class I chain-related protein A (MICA) is a membrane glycoprotein expressed abnormally on some malignant cells including gastric cancer (GC) cell and elicits anti-tumor immune responses. Downregulation of MICA expression could lead to immune-evasion of cancer cells.

Objective(s)

In this study, we aimed to investigate the effect of docosahexaenoic acid (DHA) and docetaxel alone or in combination on the expression level of MICA and its regulating microRNA (miRNA), miR-20a in MKN45 GC cell line.

Method(s)

MKN45 GC cell line was cultured and MTT assay was performed to determine IC50 of docetaxel. Cells were treated by 18.5 μM docetaxel and 100 μM DHA. After that, RNA extraction and cDNA synthesis were done and the expression level of MICA and miR-20a were determined by quantitative real-time PCR for both treated and untreated cell lines.

Results

Our findings showed less downregulation of the expression level of MICA by the combination of docetaxel/DHA (5.34-fold) compared with docetaxel (45.45-fold) and DHA (55.55-fold). Consistently, combination therapy led to the more downregulation of the expression level of the miR-20a (5.20-fold) in comparison to docetaxel (2.38-fold) and DHA (1.60-fold).

Conclusion(s)

As an unwanted effect of docetaxel therapy in GC, downregulation of MICA expression could lead to weak anti-tumor immune responses. By increasing the expression level of MICA, combination therapy of docetaxel with DHA would be useful to overcome this side effect.

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Funding

This study was done by a grant from Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (Grant No. 12095).

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Authors and Affiliations

  1. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Najibeh Shekari & Sima Ghaffari

  2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Najibeh Shekari & Sima Ghaffari

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahsa Javadian

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

    Behzad Baradaran & Tohid Kazemi

  5. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Masoud Darabi

  6. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, P.O. Box: 5165683146, Tabriz, Iran

    Tohid Kazemi

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  1. Najibeh Shekari
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Correspondence to Tohid Kazemi.

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Shekari, N., Javadian, M., Ghaffari, S. et al. DHA Abolishes the Detrimental Effect of Docetaxel on Downregulation of the MICA via Decreasing the Expression Level of MicroRNA-20a in Gastric Cancer. J Gastrointest Canc 51, 545–551 (2020). https://doi.org/10.1007/s12029-019-00280-3

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