Neddim KARAGENÇ, Duygu MEYDANCI, Hakan KÜÇÜKSAYAN

Akciğer kanseri hücre dizilerinde hipoksi indüklenebilir faktör-1 (HIF-1) ve paraoksonaz enzim ilişkisinin araştırılması

Amaç: Bu çalışmada tümör anjiyogenezinde önemli rol oynayan hipoksi indüklenebilir faktör 1 (HIF-1) transkripsi- yon faktörünün hipoksik ve normoksik koşullarda paraok- sonaz 2 (PON2) ile ilişkisinin araştırılması hedeflenmiştir. Hipoksiye duyarlı bir transkripsiyon faktör olan HIF-1α çok sayıda genin transkripsiyonunu sağlayarak anjiyoge- nez ve metastazın başlamasına yol açar. Hipoksinin yanı sıra lipopolisakkarit (LPS) gibi çeşitli inflamatuvar ajanlar da HIF-1 αnın ve PON2 nin ekspresyonunu düzenleyebi- lirler. Oksidatif stres karsinogenezde önemli etiyolojik fak- törlerden birisidir. Paraoksonaz ailesi üyelerinden paraok- sonaz 2 (PON2) nin hücre içi antioksidan olarak görev yaptığı bilinmektedir. Yöntemler: H1299, A549 ve PC14 akciğer hücre dizileri normoksi ve hipoksi ortamlarında kültürü yapılarak ve li- popolisakkaritle indüklenerek HIF-1 ve PON2 mRNA eks- presyonları ve western blot tayinleri çalışılmıştır. Bulgular: Çalışma sonucunda LPS uygulamasının HIF- 1α ekspresyonunu uyardığı ve hipoksi koşullarında akci- ğer hücre dizilerinde PON2 ekspresyonunun arttığı göz- lendi. Sonuç: Bu çalışmada PON 2 enzim ekspresyonunun HIF-1α aracılığıyla hipoksi ve normoksi koşullarında re- güle edildiği gözlenmiş olup hipoksi, inflamasyon ve hüc- renin oksidatif durumu arasındaki ilişkinin aydınlatılması için ileri çalışmalar gerekebilir.

Association of hypoxia inducible factor 1 (HIF-1) and paraoxonase enzyme in lung cancer cell lines

Objective: In this study, it was aimed to investigate that PON2, in hypoxia and normoxia in relation to HIF-1α tran- scription factor that has a role in tumour angiogenesis. Hypoxia inducible factor 1 alpha (HIF-1α) is a transcrip- tion factor which is sensitive to hypoxia, causes initiation of angiogenesis and metastasis by providing transcription of numerous genes. As well as hypoxia several inflamma- tory agents such as lipopolysaccharide (LPS) can regu- late the expression of HIF-1α as well as PON2. Oxida- tive stress is known to have role in cancer. Paraoxonase 2 which is one of the members of paraoxonase family serves as intracellular anti-oxidant. Methods: H1299, A549 ve PC14 non-small cell lung carcinoma cell lines used in this study. Cells were cul- tured under hypoxia and normoxia conditions with LPS stimulation. HIF-1α and PON2 mRNA expression levels measured by real-time PCR. Western blot studies were performed for protein expression. Results: In this study, it was observed that LPS treatment stimulates HIF-1α expression which increases PON2 ex- pression in NSCLC cell line in under hxpoxia conditions. Conclusion: This study shows that PON2 is regulated by HIF-1α in hypoxia and inflammation. The relationship between hypoxia and inflammation and oxidative status of cells requires further studies

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