A direct bridge to metformin and matrix metalloproteinase relationship in prostate cancer model: oxidative stress

Year 2022, , 360 - 365, 31.03.2022

Pınar Köroğlu

https://doi.org/10.17826/cumj.1034451

Abstract

Purpose: The purpose of the study was to evaluate the effect of metformin as well as the possible role of Matrix metalloproteinase2 (MMP2) and oxidative stress parameters on the prostate cancer model.
Materials and Methods: Male Copenhagen rats were divided into three groups. Control group, cancer group, cancer+metformin (CM) group. 2x104 Mat-LyLu cells were inoculated subcutaneously to generate prostate cancer. Metformin treatment was administered daily by gavage following inoculation of the Mat- Lylu cells. The experiment was terminated on the 14th day following Mat-LyLu cell injection. Serum glutathione (GSH), prostate-specific antigen (PSA), and malondialdehyde (MDA) levels were determined by employing the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. In addition, the serum matrix metalloproteinase (MMP) 2 activities were determined via ELISA.
Results: GSH was significantly increased in the CM group than in the cancer group. PSA, MDA and MMP2 were significantly lower in the CM group than in the cancer group. Oxidative stress parameters were significantly higher in the cancer group. Metformin reversed cancer’s effect in GSH, PSA, MDA, and MMP2 parameters.
Conclusion: Prostate cancer model caused a detrimental effect on MMP and oxidative stress parameters, and metformin administration ameliorated the changes caused by cancer. Metformin showed its mechanism of action by inhibiting free radical products originating from prostate cancer and changing the antioxidant capacity. Metformin is a candidate to be a potential anticancer drug in the therapeutic cancer treatment process.

Keywords

Matrix metalloproteinase, prostate cancer, rat, metformin, oxidative stress

Supporting Institution

by The Scientific Research Projects Coordination Unit of Istanbul University

Project Number

48418

Thanks

I am particularly grateful to my supervisor Prof. Dr. Omur Karabulut Bulan. I am thankful to her for my PhD education in the field of toxicology, oxidative stress and her great intellectual support. In addition, I am thankful to Dr. Ilknur Bugan for prostate cancer experimental period.

Prostat kanseri modelinde metformin ve matriks metalloproteinaz ilişkisine doğrudan bir köprü: oksidatif stress

Abstract

Amaç: Çalışmanın amacı, prostat kanseri modelinde metforminin etkisinin yanı sıra Matriks metalloproteinaz2 (MMP2) ve oksidatif stres parametrelerinin olası rolünü belirlemekti.
Gereç ve Yöntem: Erkek Copenhagen sıçanları üç gruba ayrıldı. Kontrol grubu, kanser grubu, kanser+metformin (CM) grubu. Prostat kanseri, 2x104 Mat-LyLu hücrelerinin subkutan enjeksiyonu ile oluşturuldu. Metformin tedavisi, Mat- Lylu hücrelerinin ardından gavaj yoluyla günlük olarak uygulandı. Mat-LyLu hücre enjeksiyonunu takiben 14. günde deney sonlandırıldı.. Enzyme Linked Immuno Sorbent Assay (ELISA) yöntemi kullanılarak serum glutatyon (GSH), prostat spesifik antijen (PSA) ve malondialdehit (MDA) düzeyleri belirlendi. Ayrıca serum matriks metalloproteinaz 2 (MMP) 2 aktiviteleri ELISA aracılığıyla belirlendi.
Bulgular: GSH, CM grubunda kanser grubuna göre önemli ölçüde arttı. PSA, MDA ve MMP2, CM grubunda kanser grubuna göre anlamlı derecede düşüktü. Oksidatif stres parametreleri kanser grubunda anlamlı olarak yüksek bulundu. Metformin GSH, PSA, MDA ve MMP2 gibi parametrelerdeki kanser etkisini tersine döndürdü.
Sonuç: Prostat kanser modelinin MMP ve oksidatif stres parametreleri üzerine zararlı bir etkiye neden olduğunu ve metformin uygulamasının da kanserin neden olduğu değişiklikleri iyileştirdiği saptandı. Metforminin etki mekanizmasını prostat kanseri kaynaklı serbest radikal ürünlerini inhibe ettiği ve antioksidan kapasiteyi değiştirerek gösterdiği belirlendi. Metformin, terapötik kanser tedavi sürecindeki potansiyel bir anti kanser ilacı olmaya adaydır.

Keywords

matriks metalloproteinaz, metformin, prostat kanser, sıçan, oksidatif stress

Project Number

48418

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