Mehmet ŞAHİN, Emel ŞAHİN, Saadet GÜMÜŞLÜ

Isı Şok Protein İnhibitörü KNK437’nin Endotel Hücrelerinde Anjiyogenez Üzerine Etkisi

Amaç: Hipertermi, kanser ve tümöral anjiyogenez için etkili bir tedavi şeklidir. Ancak, termotolerans gelişimi önemlibir problemdir. Bu çalışmada KNK437 ve quercetinin endotel hücrelerinde anjiyogenez ve termotolerans üzerineetkileri araştırıldı.Yöntem ve gereç: KNK437 veya quercetin ile ön muamele edilmiş olan endotel hücrelerine tek basamaklı ve kademelihipertermi uygulanmıştır. Bu hücrelerde anjiyogenezin incelenmesi için Matrijel Matrikste tüp oluşumu deneyigerçekleştirilmiştir.Bulgular: KNK437 veya quercetin ile 37 °C’de muamele edilmiş olan hücrelerde tüp oluşumunun baskılandığıgörülmüştür. Tek basamaklı hiperterminin (45 °C’de 1 saat) tüp oluşumunu azalttığı görülmüştür. Tüp oluşumu,KNK437 veya quercetin ile ön muamele edilmiş hipertermi grubunda, sadece hipertermi uygulanmış gruba göre düşükbulunmuştur. Kademeli hipertermi grubuna ait tüp uzunluğu anlamlı şekilde yeniden artış göstermiştir. Bununla birlikte,KNK437 veya quercetin ile ön muamele termotoleransın anjiyogenez üzerine olan etkilerini geriye döndürmüştür.Çalışılan tüm deney gruplarında KNK437’nin quercetinden daha etkili olduğu görülmüştür.Sonuç: Bu çalışma, KNK437’nin endotel hücrelerinde anjiyogenez ve termotoleransı inhibe etmesi bakımındanorjinaldir. KNK437 insan metastatik kanserlerinde uygulanan hipertermik tedavinin etkinliğine katkıda bulunabilenesansiyel bir molekül olabilir.

Anahtar Kelimeler:

angiogenesis, KNK437, quercetin, tube formation, endothelial cells, Hyperthermia

The Effect of KNK437, a Heat Shock Protein lnhibitor, on Angiogenesis of Endothelial Cells

Aim: Hyperthermia is an effective therapy for cancer and tumor angiogenesis. However, the development of thermotolerance is an important problem. We aimed to investigate the effects of KNK437 and quercetin on angiogenesis and thermotolerance in endothelial cells (ECs). Materials and methods: ECs were grown in EGM-2 medium. ECs were preincubated with KNK437 or quercetin and then treated with single and fractionated hyperthermia. Tube formation assay on Matrigel Matrix was performed in these cells to investigate angiogenesis. Results: Tube formation was suppressed in cells that were treated with KNK437 and quercetin at 37 °C. Single hyperthermia (45 °C for 1 h) inhibited tube formation. KNK437 and quercetin pretreatment decreased capillary-like structures more effectively than single hyperthermia treatment. In cells that acquired thermotolerance induced by fractionated hyperthermia, tube formation was dramatically increased, but KNK437 and quercetin reversed the effects of thermotolerance on angiogenesis. KNK437 was found to be more effective than quercetin in all study groups. Conclusion: This study is original in that KNK437 inhibited angiogenesis and thermotolerance in ECs. This compound may be an essential molecule contributing to the efficient treatment of hyperthermic therapy in human cancers.

Keywords:

angiogenesis, KNK437, quercetin, tube formation, endothelial cells, Hyperthermia,

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