A23187 Tamoksifene Dirençli Meme Kanseri Hücrelerinin Tamoksifen Duyarlılığını Geliştirebilir

Giriş ve Amaç: Tamoksifen, ER α-pozitif meme kanserinin tedavisinde en yaygın kullanılan terapötik bir ajandır. Ancak hastaların büyük bir kısmında tamoksifen’e karşı direnç kazanımının oluşması; terapötik etkinliği sınırlamakta ve hastalarda sağ kalım oranını azaltmaktadır. Hücre hareketliliği, gen ifadesi regülasyonu gibi çok sayıda kritik rolü olan Ca+2 sinyal mekanizması karsinogenez ile ilişkili proliferasyon, migrasyon, anjiyogenez ve ilaç direnci gelişimi gibi süreçler üzerinde önemli rollere sahiptir. Çalışmalarımızda yüksek oranda Ca+2 seçiciliği olan ve endoplazmik retikulumdan Ca+2 çıkışına aracılık eden kalsiyum iyonofor A23187 (kalsimisin)’nin tamoksifene dirençli meme kanseri hücrelerinde proliferasyon ve tamoksifen direnci üzerine olan etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: A23187 veya Tamoksifen ile A23187 kombine uygulamasının Tamoksifene dirençli meme kanseri hücresi MCF-7/TAMR-1’de hücre proliferasyonu üzerine olan etkisini değerlendirmek amacıyla WST-1 temelli hücre proliferasyon analizleri gerçekleştirilmiştir. Ayrıca mikroskobik incelemeler yapılarak fotoğraflanmıştır. Bulgular: A21387’nin MCF-7/TAMR-1 hücreleri üzerindeki anti-proliferatif etkinliğe sahip olduğunu göstermiştir. A23187 ile tamoksifen’in kombine uygulaması ile hücrelerdeki tamoksifen direncini sınırlandırarak sinerjistik olarak hücrelerin proliferatif kapasitesini sınırladığı belirlenmiştir. Sonuç: Bulgularımız, A23187 aracılı kalsiyum sinyalinin modülasyonunun meme kanseri hücrelerinde tamoksifen duyarlılığının ilerletilmesinde umut verici bir yaklaşım olabileceğini önermektedir.

Anahtar Kelimeler:

A23187, Kalsiyum sinyalizasyonu, Meme kanseri, Tamoksifen

A23187 May Improve Tamoxifen Sensitivity of Tamoxifen-Resistant Breast Cancer Cells

Objective: Tamoxifen is the most widely used therapeutic agent for the treatment of ER α-positive breast cancer. However, the development of resistance to tamoxifen in the majority of patients limits the therapeutic efficacy of tamoxifen and reduces the survival rate of patients. Ca+2 signaling mechanism, which has many critical roles including cell motility and gene expression regulation, has important roles in processes such as proliferation, migration, angiogenesis, and drug resistance development related to carcinogenesis. In this study, we aimed to investigate the effect of Calcium ionophore A23187 (calcimicin), which has high Ca+2 selectivity and mediates Ca+2 output from the endoplasmic reticulum, on proliferation and tamoxifen resistance in tamoxifen-resistant breast cancer cells. Materials and Methods: WST-1-based cell proliferation analyzes were performed to evaluate the effect of A23187 or Tamoxifen and A23187 combined treatment on cell proliferation in Tamoxifen-resistant breast cancer cells MCF-7/TAMR-1. In addition, microscopic examinations were performed and photographed. Results: A21387 has an antiproliferative effect on MCF-7/TAMR-1 cells. Moreover, a combined treatment of A23187 and tamoxifen synergistically reduced the proliferative capacity of cells manner dose-dependent by limiting tamoxifen resistance. Conclusion: Our findings suggest that modulation of calcium signaling by A23187 may be a promising approach to improve tamoxifen sensitivity in breast cancer cells.

Keywords:

A23187, Calcium signaling, Breast cancer, Tamoxifen,

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