Düzleştirici filtreli ve düzleştirici filtresiz ışınlar ile radyorapi sonucunda malign melanomda apoptotik, tümör baskılayıcı ve hücre bölünmesi ile ilişkili genlerin ifadesi

Öz

Amaç: Düzleştirici filtreli (FF) ve düzleştirici filtresiz (FFF) ışınların malign melanom kanseri üzerindeki etkileri in vivo olarak henüz tam olarak aydınlatılamamıştır. Bu çalışmada, FF ve FFF ışınlara yanıt olarak apoptotik, tümör baskılayıcı ve hücre proliferasyonu ile ilişkili genlerinin ifade düzeylerinin belirlenmesi amaçlanmıştır. Yöntem: Yirmi sekiz NOD-Prkdc IL2rg^tm1 (NSG) fare rastgele olarak dört gruba ayrılmıştır. Tümör enjeksiyonunu takip eden 20. günde radyoterapi uygulaması yapılmıştır. Tümör oluşturulmamış Kontrol grubu ile malign melanom kanseri (MMe Ka) grubu radyoterapi almazken; FF-400 ve FFF-1400 grupları sırasıyla FF modunda 400 MU/dk ve FFF modunda 1400 MU/dk doz hızlarında tek seferlik 20 Gy radyoterapi almıştır. BAX, BCL-2, PTEN, Ki-67 ve TNF-α genlerinin ifade düzeyleri radyoterapiden 48 saat sonra değerlendirilmiştir. Bulgular: Tüm genlerin, MMe Ka grubunda Kontrol grubuna kıyasla anlamlı derecede daha yüksek düzeyde ifade edildiği bulunmuştur (p<0.001). BAX, PTEN ve TNF-α gen ifade düzeyleri, radyoterapi uygulanan MMe Ka gruplarında farklı doz hızlarına bağlı olarak anlamlı şekilde artmıştır (p<0.001). FF-400 ve FFF-1400 grupları arasında BAX ve PTEN düzeylerinde anlamlı farklar saptanmış (p<0.001), ancak TNF-α düzeylerinde bu fark gözlenmemiştir. Ayrıca, Ki-67 ve BCL-2 gen ifade düzeyleri radyoterapi sonrası azalmıştır (p<0.001); bu azalmanın FFF ışını kullanlan daha belirgin olduğu gözlenmiştir (p<0.001). Sonuç: Bulgularımız hem FF hem de FFF ışınlarının apoptoz, tümör baskılama ve hücre proliferasyon süreçlerine ilişkin radyobiyolojik değişiklikleri etkili bir şekilde indüklediğini, ancak FFF ışınının MMe Ka üzerinde FF ışınına kıyasla daha etkin olduğunu göstermektedir.

Anahtar Kelimeler

• Malign Melanom
• Radyoterapi
• Doz Hızı
• Laboratuvar Hayvanlaı
• Gen İfadesi

The effect of flattened and unflattened beams on apoptotic, tumor suppressor, and cell proliferation gene expression levels in preclinical malignant melanoma radiotherapy

Öz

Background/aim: The current evidence base remains lacking regarding the differences in radiobiological outcomes dependent on the presence of a flattening filter in malignant melanoma cancer (MMe Ca) radiotherapy. We designed the present study to elaborate on the malignancy-related gene expression profiles in MMe Ca tumors in response to flattening filter (FF) and flattening filter-free (FFF) beams. Materials and methods: Twenty-eight NOD-Prkdc IL2rg tm1 (NSG) mice were randomly assigned to four experimental groups. The non-engrafted Control and MMe Ca groups did not receive irradiation, while the FF-400 and FFF-1400 groups received single-dose 20 Gy radiotherapy in FF (400 MU/min) and FFF modes (1400 MU/min). B-cell lymphoma 2 (BCL-2), Bcl-2-associated x protein (BAX), phosphatase and tensin homolog (PTEN), marker of proliferation Ki-67 (Ki-67), and tumor necrosis factor alpha (TNF-α) gene expression levels were evaluated 48 hours post-radiotherapy. Results: All tested genes were significantly upregulated in the MMe Ca group compared with the Control group (p < .001). Expressions of BAX, PTEN, and TNF-α were significantly higher (p < .001) in the MMe Ca plus radiotherapy groups, depending on the different dose rates. Significant differences in BAX and PTEN levels were found in response to FF and FFF beams (p < .001). Ki-67 and BCL-2 were decreased after radiotherapy (p < .001), with the FFF beam exerting a more prominent effect than the FF beam (p < .001). Conclusion: Our results indicate that both FF and FFF beams effectively induce radiobiological changes regarding apoptosis, tumor suppression, and cell proliferation processes, while the FFF beam is superior to the FF beam in MMe Ca.

Anahtar Kelimeler

• Malignant Melanoma
• Radiotherapy
• Dose Rate
• Laboratory Animals
• Gene Expression

Kaynakça

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