Ishikawa Endometrial Kanser Hücre Kültüründe Bevacizumabin Tek Başına ve Klasik Kemoteropatiklerle Birlikte Kullanımı

Amaç: Çalışmamızın amacı anti anjiogenik ajanların (bevacizumab) endometriyum kanserinde klasik kemoterapilerle kombine ve tek başına kullanımlarının etkilerini araştırmak ve klinik pratiğe yansıtmaktır. Gereç ve Yöntem: Cisplatin, Adriablastin, Bevacizumab kombinasyonlarının sitotoksik ve apoptotik etkilerini saptamak için in vitro testler yapılmıştır. Bunun için Ishikawa (insan endometriyum kanser hücresi) hücre kültürü üzerinde sitotoksik etkiyi belirlemek için MTT testi (Tetrozolium Testi), apoptosizi saptamak için ise DAPI boyama, caspase–3 testi kullanılmıştır. Bulgular: Bevacizumabın 9,6 mg/ml’lık dozunun Ishikawa hücreleri üzerinde Cisplatin ve Adriablastinin en yüksek dozlarına göre hücre sayısında daha yüksek bir oranda düşüşe neden olduğu MTT testi ile belirlenmiştir. Aynı zamanda Bevacizumab, Cisplatin ve Adriablastininin 24 saat birlikte uygulandığında doz artışı ile hücre sayısında azalma meydana gelmiştir. DAPI boyama ile üçlü kombinasyonun kullanımı ile hücre silüetlerinin silindiği ve apoptozisi gösteren bulguların daha bariz hale geldiği görülmektedir. Bevacizumab tek başına uygulandığında oluşturduğu kaspaz 3 aktivitesi diğer iki ilacın tek tek ve ikili kombinasyonundan daha yüksek bulunmuştur. 40 µM Cisplatin + 20 µM Adriablastin + 9,6 µgram/ ml Bevacizumabın birlikte uygulanması sonucunda kaspaz-3 aktivitesinin önemli ölçüde artış gösterdiği saptanmış ve bu diğer uygulamalarla kıyaslandığında en yüksek sitotoksik aktivite olarak bulunmuştur. Sonuç: Bevacizumab yalnız başına veya diğer kemoterapötüklerle birlikte önemli antikanser etkiye sahiptir.Anahtar Kelimeler: Endometrium kanseri, angiogenezis, VEGF, Ishikawa, apoptosiz.

The Use of Bevacizumab Alone and in Combination with Classical Chemotheropathics in Ishikawa Endometrial Cancer Cell Culture

Purpose: The aim of our study is to determine the effects of an antiangiogenic agent (bevacizumab) in combination with or without classic chemotherapeutics on the endometrium carcinoma and use these information in our clinic practice. Materials and Methods: In vitro tests were done to determine the cytotoxic and apoptotic effects of Cisplatin, Adriablastine and Bevacizumab. Cytotoxic effect was determined by the standard MTT assay (Tetrozolium Test) and apopthosis by DAPI staining, caspase-3 on human endometrium cancer cell culture (Ishikawa). Results: The MTT assay determined that 9.6 mg/ml dose of bevacizumab caused a higher rate of decrease in cell number on Ishikawa cells compared to the highest doses of Cisplatin and Adriablastine. Therewithal, when Bevacizumab, Cisplatin, and Adriablastine were applied together for 24 hours, the number of cells decreased with an increasing dose. With the use of the triple combination with DAPI staining, it is seen that the cell silhouettes are effaced and the findings indicating apoptosis become more apparent. When bevacizumab was applied alone, the caspase 3 activity it produced was ascertained to be higher than the other two drugs individually and in combination. Caspase-3 activity was ascertained to have increased significantly as a result of the collective usage of 40 µM Cisplatin + 20 µM Adriablastine + 9.6 µgram / ml Bevacizumab, and this was found to be the highest cytotoxic activity compared to other applications. Conclusion: Bevacizumab has significant anticancer activity alone or in combination with other chemotherapeutics.Keywords: Endometrial carcinoma, angiogenesis, VEGF, Ishikawa, apoptosis.

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Acıbadem Üniversitesi Sağlık Bilimleri Dergisi-Cover
  • ISSN: 1309-470X
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2010
  • Yayıncı: ACIBADEM MEHMET ALİ AYDINLAR ÜNİVERSİTESİ