5-FLOROURACİL VE RESVERATROL KOMBİNASYONUNUN İNSAN AKCİĞER KANSERİ A549 HÜCRE HATTINDA APOPTOZİS ÜZERİNE ETKİSİ

Amaç: 5-Florourasil (5-FU), göğüs, mide, özofagus ve pankreas kanseri dahil olmak üzere çeşitli kanser türlerinde kullanılan bir kemoterapi ilacıdır. Resveratrol (RES), flavon olmayan polifenolik bir bileşiktir ve çeşitli kanser türlerinde kemoterapötik etkisi bulunmaktadır. 5-FU ve RES'in etkilerinin tek başına kapsamlı bir şekilde araştırılmasına rağmen, RES ile kombine edilen 5-FU'nun A549 hücre hattı üzerine etkisi hala bilinmemektedir. Bu çalışmada, A549 akciğer kanseri hücre hattında 5-FU ve RES kombinasyonunun apopitotik yolak üzerindeki etkisi araştırılmıştır. Gereç ve Yöntemler: 5-FU ve RES kombinasyonunun A549 akciğer kanseri hücreleri üzerindeki etkisini belirlemek için, Water Soluble Tetrazolium-1 (WST-1) deneyi ile hücre canlılığı, 2’,7’–dichlorofluorescin diacetate (DCFDA) kiti ile ROS seviyesi, klonojenik deney ile hücrelerin koloni oluşturma kabiliyeti, Western blot ile pro-apoptotik Bax ve TP53 kaynaklı glikoliz ve apopitozis düzenleyicisi (TIGAR) proteinlerin ekspresyon düzeyleri analiz edilmiştir. Bulgular: 5-FU ve RES kombinasyonu, A549 hücre hattının hücre canlılığını ve koloni oluşturma potansiyelini önemli ölçüde azaltmıştır. Dahası, Western Blot analizi, 5-FU ve RES kombinasyonunun pro-apopitotik Bax proteininin artmasına neden olduğunu, TIGAR protein ekspresyon seviyesinin ise konsantrasyona bağlı bir şekilde azaldığını göstermiştir. Sonuç: Sonuçlarımız, Resveratrolün A549 hücre dizisinde 5- FU'nun anti-tümör etkisini artırabileceğini göstermiştir.

The Effect of 5-Florouracil and Resveratrol Combination on Apoptosis in A549 Human Lung Cancer Cell Line

Objective: 5-Fluorouracil (5-FU) is a chemotherapy drug used in various cancers including breast, stomach, esophageal and pancreatic cancer. Resveratrol (RES) is a well known nonflavon polyphenolic compound that has chemotherapeutic effect in various types of cancer. Despite the fact that effects of 5-FU and RES alone have been extensively studied in the past few years, the effect of 5-FU combined with RES in the A549 cell line remains unknown. In this study, we investigated the effect of combination of RES and 5-FU on apoptotic pathway in A549 lung cancer cell line. Material and Methods: The effect of of 5-FU and RES combination on A549 lung cancer cells was examined by cell viability using Water Soluble Tetrazolium-1 (WST-1) assays, by ROS level using 2’,7’–dichlorofluorescin diacetate (DCFDA) assay and by the ability of cells to form colonies by clonogenic assay, pro-apoptotic Bax and TIGAR protein expression using Western Blotting analysis. Results: Combination of 5-FU and RES significantly decreased cell viability and clonogenic potential of A549 cell line. Furthermore, Western Blotting analysis showed that 5-FU and RES combination caused pro-apoptotic Bax protein to increase, while TIGAR protein expression level decreased in concentration-dependent manner. Conclusion: Our results suggested that resveratrol can increase the anti-tumor effect of 5-FU in A549 cell line.

Kaynakça

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