INVESTIGATION OF THE EFFECTS OF METFORMIN ON THE miR- 21/PTEN/Akt PATHWAY IN HT-29 HUMAN COLORECTAL ADENOCARCINOMA CELL AND HUVEC CO-CULTURE
Yazarlar (7)
Doç. Dr. Çiğdem SEVİM Kastamonu Üniversitesi, Türkiye
Doç. Dr. Alı Taghızadehghalehjoughı Bilecik Şeyh Edebali Üniversitesi, Türkiye
Doç. Dr. Mehtap Kara İstanbul Üniversitesi, Türkiye
Alexander Nosyrev
Sechenov First Moscow State Medical University, Rusya Federasyonu
George Mıhaı Nıtulescu
Universitatea De Medicina Si Farmacie Carol Davila Din Bucuresti, Romanya
Denısa Margına
Universitatea De Medicina Si Farmacie Carol Davila Din Bucuresti, Romanya
Arıstıdes Tsatsakıs
University of Crete, Yunanistan
Makale Türü Açık Erişim Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
Dergi Adı Farmacia (Q4)
Dergi ISSN 0014-8237 Dergi Bilgileri (2024)
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce Basım Tarihi 01-2024
Kabul Tarihi Yayınlanma Tarihi 29-02-2024
Cilt / Sayı / Sayfa 72 / 1 / 60–65 DOI 10.31925/farmacia.2024.1.5
Makale Linki https://farmaciajournal.com/article-archive/current-issue/
UAK Araştırma Alanları
Tıbbi Farmakoloji
Özet
Colon adenocarcinoma is a major cause of cancer mortality worldwide. Type 2 diabetic people have an increased risk of developing colorectal cancer compared with nondiabetic people. There are studies showing that metformin inhibits angiogenesis, which is an important stage in cancer metastasis. Our aim was to identify the effects of metformin on miR-21, PTEN, and Akt gene expressions associated with angiogenesis in co‐culture conditions established with human colorectal adenocarcinoma cells (HT-29) and human umbilical vein endothelial (HUVEC) cells. Cytotoxicity was evaluated via MTT assay, and PTEN, Akt, and miR-21 expressions were measured by real-time polymerase chain reaction in HUVEC cells under the effects of HT29 cells. Cell viability decreased with increasing doses of metformin, especially in the 160 µg/mL metformin treatment group. According to real-time PCR results, PTEN was significantly upregulated in 80 and 160 µg/mL metformintreated cells, and Akt, and miR-21 expressions were downregulated significantly in all metformin treatment groups. An inverse relation was found between PTEN, Akt and miR-21 levels in HUVEC cells under HT29-HUVEC co-culture conditions. Increased PTEN signalling was associated with the prevention of angiogenesis through reducing cell proliferation and migration. The miR‑21/PTEN/Akt signalling pathway may have a crucial role in the molecular mechanism of metformin's antiangiogenic effect.
Anahtar Kelimeler
Akt | HUVEC. HT-29 | metformin | miR-21 | PTEN