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Synergistic Beneficial Effect of Docosahexaenoic Acid (DHA) and Docetaxel on the Expression Level of Matrix Metalloproteinase-2 (MMP-2) and MicroRNA-106b in Gastric Cancer

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Abstract

Background

Gastric cancer (GC) is one of the most common cancers with the majority of patients recognized in advanced stages. The efficacy of using docosahexaenoic acid (DHA) as a supplementary agent has been suggested in treatment along with chemotherapeutics including docetaxel. However, the molecular signatures of such beneficial effects are not well-understood.

Objective(s)

We aimed to evaluate the effects of DHA and docetaxel on the expression level of metastasis-related genes, including MMP-2 and talin-2, and their controlling miRNAs, miR-106b and miR-194, in metastatic GC cell line, MKN45.

Method(s)

GC cell line, MKN45, was cultured, and determination of IC50 of DHA was done by MTT test. Cells were treated with docetaxel, DHA, and their combination for 24 h, and then total RNA was extracted and cDNA synthesis was done using standard protocols. The expression level of target genes, MMP-2 and talin-2, and miR-106b and miR-194 were determined by using quantitative real-time PCR.

Results

The expression level of MMP-2 was decreased significantly in all treated cells. However, talin-2 showed significant downregulation only after treatment with docetaxel. In contrary to increased expression after treatment with docetaxel, DHA led to a significant under-expression of miR-106b. The similar effect was seen for miR-194.

Conclusion(s)

Combination of docetaxel and DHA led to the significant downregulation of MMP-2. Also, DHA lowered the docetaxel-mediated upregulation of miR-106b oncomiR. In conclusion, supplementation of docetaxel therapy with DHA in GC patients would be considered as a beneficial approach in cancer treatment.

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Funding

This study was done by a grant from Infectious and Tropical Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran. (Grant number: 13098).

Author information

Authors and Affiliations

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

    Najibeh Shekari & Mottahareh Ghasemi

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

    Najibeh Shekari & Mottahareh Ghasemi

  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., Ghasemi, M. et al. Synergistic Beneficial Effect of Docosahexaenoic Acid (DHA) and Docetaxel on the Expression Level of Matrix Metalloproteinase-2 (MMP-2) and MicroRNA-106b in Gastric Cancer. J Gastrointest Canc 51, 70–75 (2020). https://doi.org/10.1007/s12029-019-00205-0

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