Sakarya Medical Journal

2146-409X

Sakarya University

10.31832/smj.511954

Assessment of the Therapeutic Effects of Zoledronic Acid on Breast Cancer Subtypes

Zoledronik Asidin Meme Kanseri Alt Tiplerinde Terapötik Etkisinin Değerlendirilmesi

https://orcid.org/0000-0002-2088-9914

Güney Eskiler

Gamze

SAKARYA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ Deveci Özkan

Asuman

SAKARYA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ Bilir

Cemil

SAKARYA ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ Kaleli

Süleyman

SAKARYA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ

03 20 2019

9 1 92 102 01 11 2019 01 25 2019

2011

Sakarya Medical Journal

Objective:Breast cancer is a heterogeneous type of cancer with many subtypes and is themost common cancer among women. It is noteworthy that breast cancersubtype-based treatment options have attracted great attention. In the presentstudy, we aimed to investigate the therapeutic effect of a bisphosphonateinhibitor zoledronic acid (ZOL), which is aclinically used in the treatment of cancer types with bone metastases and hasbeen found to exert anti-proliferative and anti-metastatic effects, on twodifferent subtypes of breast cancer [MCF-7 (ER+, PR+, HER2-) and MDA-MB-231(ER-, PR-, HER2-)] and HUVEC control cells. Materials and Methods: Thecytotoxic and apoptotic effect of ZOL (10-100 uM) for 24 and 48 hours wasdetermined by WST-1, Annexin V and cell cycle analysis. In addition, changes incell morphology and nucleus after treatment with ZOL observed by acridine orange(AO) and DAPI staining, respectively.Results:ZOL caused more anti-proliferative effect and early and late apoptotic death inMDA-MB-231 cells compared with MCF-7 cells (p<0.05).The cell population in G0/G1 phase was significantlyincreased after treatment with especially 50 and 100 µM ZOL (p <0.05). Additionally, the loss of cell membraneintegrity and chromatin condensation were observed in MCF-7 and MDA-MB-231cells treated with ZOL. However,ZOL had a toxic effect on HUVEC cells at higher concentrations.Conclusion:In conclusion, although ZOL has a potential therapeutic effect on differentsubtypes of breast cancer, ZOL causes more cytotoxic effects and apoptoticdeath in triple negative breast cancer (MDA-MB-231) cells than hormonesensitive (MCF-7) cells. However, further studies are needed to determine themolecular mechanisms underlying the therapeutic effect of ZOL depending on subtypesof breast cancer and the optimal schedule and dose of ZOL.

Amaç: Memekanseri kadınlarda en sık görülen ve farklı alt tiplere ayrılan heterojen bir kansertürüdür. Bu nedenle, meme kanseri alt tiplerine özgü tedavi yaklaşımları dikkatçekmektedir. Mevcut çalışmada, kemik metastazı görülen kanser tiplerinintedavisinde klinikte kullanılan ve anti-proliferatif, ve anti-metastatik etkiyesahip olduğu bilinen bir bifosfonat inhibitörü zoledronik asitin (ZOL)’ün, ikifarklı meme kanseri alt tipinde [MCF-7 (ER+, PR+, HER2-) ve MDA-MB-231 (ER-,PR-, HER2-)] ve HUVEC kontrolhücrelerinde terapötik etkisinin araştırılması amaçlanmıştır.Gereç ve Yöntem:ZOL’ün (10-100 µM) 24 ve 48 saat boyunca sitotoksik ve apoptotik etkisi WST-1,Annexin V ve hücre siklusu analizleri ile belirlenmiştir. Ayrıca ZOL’ün, hücrelerde ve nukleusda nedenolduğu morfolojik değişimler sırasıyla akridin oranj (AO) ve DAPI boyaması ilegörüntülenmiştir. Bulgular: ZOL’ün MCF-7 hücrelerine göre, MDA-MB-231 hücrelerinde daha fazlaanti-proliferatif etkiye ve erken ve geç apoptotik ölüme neden olduğu analizedilmiştir (p<0.05). Özellikle 50 ve100 µM ZOL uygulanan hücrelerdeG0/G1 fazında hücre miktarının anlamlı bir şekilde arttığı saptanmıştır(p<0.05). Bunun yanı sıra, ZOL uygulanan MCF-7 ve MDA-MB-231 hücrelerinde, hücremembran bütünlüğünde bozulma ve kromatin yoğunlaşması gözlemlenmiştir. Ancak,yüksek konsantrasyonlarda ZOL’ün HUVEC hücrelerinde toksik etkiye neden olduğubelirlenmiştir. Sonuç: Sonuçolarak, ZOL’ün farklı meme kanseri alt tiplerinde potansiyel terapötik etkiyesahip olduğu belirlenmekle birlikte, triple negatif meme kanseri (MDA-MB-231)hücrelerinde, hormon duyarlı (MCF-7) hücrelere göre daha fazla sitotoksiketkiye ve apoptotik ölüme neden olduğu tespit edilmiştir. Ancak, ZOL’ün meme kanseri alt tipine bağlı olarakdeğişen terapötik etkisine neden olan moleküler mekanizmaların ve idealuygulama protokolünün belirlenmesine yönelik detaylı çalışmalara ihtiyaçbulunmaktadır.

Meme kanseri meme kanseri alt tipleri zoledronik asit apoptoz

Breast cancer Breast cancer subtypes Zoledronic acid Apoptosis

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