İsmail Mert ALKAÇ, Murat İŞBİLEN, Barış KÜÇÜKKARADUMAN, Ali Osmay GÜRE, Burçak VURAL

ÜÇLÜ NEGATİF MEME KANSERİNDE (TNBC), AZD7762 İLACINA KARŞI HASSASLIĞIN RBFOX2 GEN EKSPRESYONU İLE ARAŞTIRILMASI

Amaç Üçlü negative meme kanseri (ÜNMK), meme kanserleri arasında en agresif, metastatik ve prognozu kötü takip eden gruptur. ÜNMK’ne karşı moleküler hedefe yönelik standart bir tedavi yaklaşımı henüz mevcut değildir. Bu nedenle yeni terapötikler geliştirilmelidir. Bu çalışmada, AZD7762'nin birkaç meme kanseri hücre hattı üzerindeki etkisini belirlemeyi ve bu ilaca duyarlılığı göstermek için bir belirteç olarak RBFOX2 gen ekspresyon düzeylerini değerlendirmeyi amaçladık. Materyal ve metod AZD7762'nin meme kanseri hücre dizileri üzerindeki sitotoksik etkisi Sulforhodamine B yöntemi ile belirlendi. RBFOX2 geninin ekspresyon seviyeleri qPCR ile belirlendi. Seçilen ilaç AZD7762'nin IC50 değerleri ile RBFOX2 ekspresyonu arasındaki korelasyonu değerlendirmek için Pearson r korelasyon analizi yapıldı. Bulgular ÜNMK ve ÜNMK olmayan grupların IC50 değerleri arasında anlamlı bir fark olmamasına rağmen, ÜNMK hücre hatlarının AZD7762'ye daha duyarlı olma eğiliminde olduğu belirlendi. Ek olarak, AZD7762'ye daha fazla duyarlılık gösteren hücrelerde artan RBFOX2 ekspresyon seviyelerinin tespit edildi. Sonuçlar RBFOX2 geninin AZD7762 etkinliğini göstermek için bir biyobelirteç olarak kullanılabileceği sonucuna varılmıştır. AZD7762'nin etkisiyle ilişkili potansiyel sinyal mekanizmalarını araştırmak için daha fazla çalışmaya ihtiyaç vardı.

Anahtar Kelimeler:

Üçlü negatif meme kanseri, RBFOX2, AZD7762, Biyobelirteç

Investigation of Sensitivity to AZD7762 in Triple-Negative Breast Cancer (TNBC) with RBFOX2 Gene Expression as a Biomarker

Objective: Triple negative breast cancer (TNBC) is one of the most metastatic, aggressive with poor prognosis types of breast cancers. There is currently no standard molecular-targeted treatment for TNBC. Therefore, new therapeutics should be developed. The aim of this study was to determine the effect of AZD7762 on several breast cancer cell lines and evaluate the RBFOX2 gene expression levels as a marker to show sensitivity to this drug.Materials and Methods: The cytotoxic effect of AZD7762 on breast cancer cell lines was determined by sulforhodamine B method. The expression levels of RBFOX2 gene were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The association between the IC50 values of the selected drug AZD7762 and RBFOX2 expression levels was evaluated by using Pearson r correlation analysis.Results: Although there was no significant difference between the IC50 values of TNBC and non-TNBC groups, it was determined that TNBC cell lines tended to be more sensitive to AZD7762. In addition, it was obvious that increasing levels of RBFOX2 expression were detected in cells that showed more sensitivity to AZD7762. Conclusion: It was concluded that the RBFOX2 gene can be used as a biomarker to show AZD7762 efficiency. Further studies are needed to investigate the potential signaling mechanisms that are associated with the effect of AZD7762.

Keywords:

Triple Negative Breast Cancer, AZD7762, RBFOX2, Biomarker,

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Yayın Aralığı: Yılda 3 Sayı
Başlangıç: 2011
Yayıncı: İstanbul Üniversitesi

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