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

Yıl 2020, Cilt: 13 Sayı: 1, 9 - 18, 21.01.2020

Berrin Tuğrul Merve İşseven

https://doi.org/10.31362/patd.623005

Öz

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.

Anahtar Kelimeler

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

Destekleyen Kurum

Manisa Celal Bayar University Scientific Research Foundation.

Proje Numarası

FBE 2016-133.

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

Proje Numarası

FBE 2016-133.

Kaynakça

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