DEBIO 1143’ün tek başına veya tamoksifenle kombinasyonunun östrojen reseptörü pozitif meme kanseri hücre hatlarındaki etkisi.

Öz

Amaç: Tamoxifen (TAM) ve DEBIO 1143 (AT-406)’ün artan konsantrasyonlarının tek başına veya birlikte uygulanmasının, MCF-7 ve BT-474 östrojen reseptörü pozitif (ER+) meme kanseri hücre hatlarındaki etkisini araştırmak.

Gereç ve Yöntem: XTT testi, Tamoxifen ve DEBIO 1143’ün tek başına veya birlikte kullanımın 72 saatlik MCF-7 ve BT-474 hücre hatlarındaki hücre canlılığı üzerine olan etkisini belirlemek için kullanıldı. TAM ve DEBIO 1143'ün tek başına / kombinasyonunun her iki hücre hattı üzerindeki etkisini göstermek için çok parametreli apoptoz analiz kiti kullanıldı ve floresan mikroskobik görüntüleme yapıldı.

Bulgular: TAM'ın IC₅₀ değeri MCF-7 ve BT-474 hücre hatlarında sırasıyla 3,8±0,6 mikromolar (µM) ve 18,9±6,7 µM idi. DEBIO 1143'ün IC₅₀ değeri, MCF-7 hücre hattında 15±0,5 uM idi. İlaç kombinasyonuna bağlı sonuçlar her iki hücre hattı için istatistiksel olarak anlamlıydı (p<0,001). Hücre canlılığının azalması apoptozis ile ilişkili bulunmadı.

Sonuç: ER+ meme kanseri hücre hatlarında, kombinasyon halinde uygulanan TAM ve DEBIO 1143 dozlarının, tek başına uygulanmalarına göre hücre canlılığını daha fazla azalttığı belirlenmiştir. Her iki hücre hattında kombinasyon dozlarının uygulanması sinerjik bir etki göstermiştir. Kombine uygulamanın sebep olduğu hücre canlılığındaki azalmanın, apoptoz dışındaki hangi hücre ölüm tipi ile olduğunu belirlemek için ileri araştırmalara ihtiyaç vardır.

Anahtar Kelimeler

• DEBIO 1143,ER + meme kanseri,SMAC mimetik,Tamoxifen

The effect of DEBIO 1143 usage alone or in combination with Tamoxifen on estrogen receptor positive breast cancer cell lines.

Abstract

Purpose: To investigate the effect of increased concentrations of Tamoxifen (TAM) and DEBIO 1143 (AT-406) administered alone or in combination on cells in MCF-7 and BT-474 estrogen receptor positive (ER +) breast cancer cell lines.

Materials and Methods: The effect of Tamoxifen and DEBIO 1143 administered alone or in combination on cell viability in MCF-7 and BT-474 cell lines at the 72nd hour was assessed by the XTT test. Multi-parameter apoptosis assay kit was used to display the effect of the alone/combination of TAM and DEBIO 1143 on both cell lines. Fluorescence microscobic analysis was performed.

Results: The IC₅₀ value of TAM was 3.8±0.6 micromolar (µM) and 18.9±6.7 µM in the MCF-7 and BT-474 cell lines, respectively. The IC₅₀ value of DEBIO 1143 was 15±0.5 µM in the MCF-7 cell line. The results related to drug combination were statistically significant for both cell lines (p<0.001). The decrease in cell viability was not associated with apoptosis.

Conclusion: In ER + breast cancer cell lines, the combined doses of the TAM and DEBIO 1143 reduced cell viability more than their administration alone. Combined administrations in both cell lines were concluded in a synergistic effect. Further research is needed to determine which cell death type other than apoptosis is associated with a reduction in cell viability caused by combined administration.

Keywords

• DEBIO 1143,ER + breast cancer,SMAC mimetic,Tamoxifen

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