Gemsitabin Uygulanan Prostat Kanseri Hücre Hatlarında Oxaliplatin ve Sisplatinin Kemoterapötik Etkilerinin Belirlenmesi

Öz

Ürogenital kanserler içerisinde erkeklerde görülme sıklığı açısından ilk sırada yer alan prostat kanseri, kanser ilişkili ölümler arasında ikinci sırada yer almaktadır. Mevcut araştırmalar, spesifik hasta popülasyonlarında ilave avantajlar sağlamak için platin-temelli kemoterapötikler ile hedeflenmiş tedavi kombinasyonlarına odaklanmıştır. Cerrahi veya radrasyonu takiben platin bazlı kombinasyon kemoterapisi kullanımı en fazla yararı sağlamaktadır. Bu çalışmanın amacı, platin temelli kemoterapötikler sisplatin ve oksaliplatin ile Gemsitabinin tek başına ve kombine dozlarının insan prostat kanserli hücre hatları olan DU-145 ve PC3 üzerindeki hücre proliferasyonu ve apoptotik yolaklar üzerine etkilerini belirlenmektedir. Prostat kanserli hücre hatlarında bu ilaçların tek başlarına veya kombine dozlarının, hücrelerin canlılığı üzerine olan etkileri WST-1 yöntemiyle ve CASP3, CASP8 ve CASP9 genlerinin mRNA düzeylerinde ifadelenme değişiklikleri RT-PCR ile belirlendi. Sonuç olarak, içsel ve dışsal yolakta görev alan CASP8 ve CASP9 genlerinin mRNA düzeyleri değerlendirildiğinde sisplatinin içsel yolaktan (CASP9) ve oxaliplatinin ise dışsal yolaktan (CASP8) apoptozu indüklediği tespit edildi. Bu göstermektedir ki; platin temelli kemoterapötik olan oxaliplatin ve sisplatin hedef yolakta farklı proteinler üzerinden etki etmektedir. Oxaliplatinin tek başına veya gemsitabin ile kombinasyonlarının apoptotik yolakta sisplatinden daha etkin olduğunu belirlendi.

Anahtar Kelimeler

• Gemsitabin,Kaspazlar,Oxaliplatin,Prostat kanseri,Sisplatin

The Determination of Chemotherapeutic Effects of Oxaliplatin and Cisplatin In The Prostate Cancer Cell Lines Administered Gemcitabine

Öz

While prostate cancer takes first place in terms of prevalence among genitourinary cancers in men, it is second among cancer related deaths. Current researches are focused on combining targeted therapy with platinum-based chemotherapy for achieve additional avantages for spesific patient populations. Use of platin-based combination chemotherapy followed by surgical resection and/or radiation ensures the most benefit terapy. The aim of this study was to compare the effectiveness of platinum-based chemotherapeutics Cisplatin and Oxaliplatin used single or combination doses with Gemsitabine on apoptosis and cell proliferation of DU145 and PC3 human prostate cancer cell lines. The effects of drugs alone or combinations on cell viability were determined by WST-1 method. The mRNA expression levels of Caspase-3, Caspase-8, Caspase-9 genes were analyzed by real time polymerase chain reaction (RT-PCR). As a result, when evaluated the mRNA levels of Caspase-8 and Caspase-9 genes that play role intrinsic and extrinsic pathway, it was faund that Cisplatin induced apoptosis by intrinsic pathway, and Cisplatin induced apoptosis by extrinsic pathway. It is determined that, only Oxaliplatin or along with Gemsitabin combinations are more effective on apoptotic pathway than Sisplatin.

Anahtar Kelimeler

• Gemsitabine,Caspases,Oxaliplatin,Prostate cancer,Cisplatin

Kaynakça

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