Akciğer kanserinde borik asitin apoptotik etkisinin incelenmesi
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Dosyalar
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İstinye Üniversitesi / Sağlık Bilimleri Enstitü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Akciğer kanseri, dünyada en çok görülen kanser türü olup, kansere bağlı ölüm sebepleri arasında birinci sırada bulunmaktadır. Akciğer kanserine çözüm bulunması amacıyla, tedaviye yönelik çalışmalar yapılmakta, farklı ilaç ve maddelerin bu hastalık üzerindeki etkileri yoğun bir şekilde araştırılmaktadır. Apoptoz, homeostazı ve organizmanın hayatta kalmasını destekleyen önemli ve gerekli bir hücre ölüm programıdır. Ancak düzensizleştiğinde, nörodejeneratif hastalıklardan kansere kadar sayısız patolojiye yol açabilmektedir. Bu nedenle apoptoz; kanser gelişiminin inaktivasyonu için önemli bir rol oynamaktadır. Bu çalışmada, akciğer kanseri hücre dizisinde (A549) borik asit kullanımının anti-proliferatif ve apoptotik etkilerinin araştırılması amaçlanmıştır. Hücre titrasyon testi xCELLigence yöntemi ile; hücre canlılığı SRB testi ile incelenmiştir. Borik asitin apoptotik aktivitesi biyokimyasal (AnnexinV) ve moleküler (qRT-PCR analizi) olarak değerlendirilmiştir. A549 ve BEAS-2B hücre hatlarına borik asitin farklı konsantrasyonları uygulandı. SRB testi ile borik asitin hücre proliferasyonunda %50 azalmaya neden olan inhibitör konsantrasyonu yani IC50 dozu ve 48. ve 72. saatteki sitotoksik etkisi belirlendi. IC50 değerlerine en yakın olan dozlar (10 mM, 20 mM, 50 mM) seçilerek ileri analizlere devam edildi. Belirlemiş olduğumuz borik asit dozları ile 12 ve 24 saat muamele edilen hücrelerden RNA izolasyonu ve cDNA sentezi yapıldı. CASP3, CASP8, CASP9, BCL2, BAX, BAD, FADD, CYCS genlerinin ekspresyon seviyeleri Real Time PCR ile incelendi. Sonuçlarımız borik asitin, kontrol grubu ile kıyaslandığında dozlarla orantılı olarak A549 hücre hattında hücre canlılığını baskıladığını gösterdi. Borik asit, bazı dozlarında CASP3, CASP8, CASP9, BAX, BAD, FADD ve CYCS genlerinin ekspresyon seviyelerini arttırmış olup BCL2 gen ifadesini azaltmıştır. Bu bulgu ile borik asitin ekstrinsik ve intrinsik yolağı tetikleyerek A549 kanser hücre hattını apoptoza teşvik ettiği saptanmıştır. Sonuç olarak, borik asitin A549 hücreleri üzerinde gösterdiği apoptotik ve anti-proliferatif etkileri nedeniyle akciğer kanseri tedavisinde bir anti-kanser ajan olarak potansiyel teşkil ettiği düşünülmektedir.
Lung cancer is the most common type of cancer and ranks first among the causes of cancerrelated death in the world. In order to find a solution to lung cancer, studies are carried out for treatment, and the effects of different drugs and substances on this disease are intensively investigated. Apoptosis is an important and necessary cell death program that promotes homeostasis and survival of the organism. But when dysregulated, it can lead to numerous pathologies, from neurodegenerative diseases to cancer. Therefore, apoptosis plays an important role in the inactivation of cancer development. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of boric acid use in the lung cancer cell line (A549). Cell titration test xCELLigence method, cell viability was examined by SRB assay. Then, the apoptotic activity of boric acid was evaluated as biochemical (Annexin-V) and molecular (qRTPCR analysis). In the study, different concentrations of boric acid were applied on the A549 and BEAS-2B cell lines. With the SRB test, the inhibitory concentration of boric acid caused a 50% decrease in cell proliferation, namely the IC50 dose and its cytotoxic effect at the 48th and 72nd hours were determined. Further analyzes were continued by selecting 10 mM, 20 mM and 50 mM doses, which are the closest doses that provide 50% viability. After 12 and 24 hours, RNA isolation and cDNA synthesis were performed from the cells treated with the boric acid doses we determined, and the expression levels of CASP3, CASP8, CASP9, BCL2, BAX, BAD, FADD, CYCS genes were examined by Real-Time PCR. Our results showed that boric acid suppressed cell viability in the A549 cell line proportionally with doses compared to the control group. Boric acid increased the expression levels of CASP3, CASP8, CASP9, BAX, BAD, FADD, and CYCS genes and decreased BCL2 gene expression at some doses. With this finding, it was determined that boric acid triggered the extrinsic and intrinsic pathways and promoted apoptosis of the A549 cancer cell line. In conclusion, we can say that boric acid has the potential as an anti-cancer agent in the treatment of lung cancer due to its apoptotic and anti-proliferative effects on A549 cells.
Lung cancer is the most common type of cancer and ranks first among the causes of cancerrelated death in the world. In order to find a solution to lung cancer, studies are carried out for treatment, and the effects of different drugs and substances on this disease are intensively investigated. Apoptosis is an important and necessary cell death program that promotes homeostasis and survival of the organism. But when dysregulated, it can lead to numerous pathologies, from neurodegenerative diseases to cancer. Therefore, apoptosis plays an important role in the inactivation of cancer development. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of boric acid use in the lung cancer cell line (A549). Cell titration test xCELLigence method, cell viability was examined by SRB assay. Then, the apoptotic activity of boric acid was evaluated as biochemical (Annexin-V) and molecular (qRTPCR analysis). In the study, different concentrations of boric acid were applied on the A549 and BEAS-2B cell lines. With the SRB test, the inhibitory concentration of boric acid caused a 50% decrease in cell proliferation, namely the IC50 dose and its cytotoxic effect at the 48th and 72nd hours were determined. Further analyzes were continued by selecting 10 mM, 20 mM and 50 mM doses, which are the closest doses that provide 50% viability. After 12 and 24 hours, RNA isolation and cDNA synthesis were performed from the cells treated with the boric acid doses we determined, and the expression levels of CASP3, CASP8, CASP9, BCL2, BAX, BAD, FADD, CYCS genes were examined by Real-Time PCR. Our results showed that boric acid suppressed cell viability in the A549 cell line proportionally with doses compared to the control group. Boric acid increased the expression levels of CASP3, CASP8, CASP9, BAX, BAD, FADD, and CYCS genes and decreased BCL2 gene expression at some doses. With this finding, it was determined that boric acid triggered the extrinsic and intrinsic pathways and promoted apoptosis of the A549 cancer cell line. In conclusion, we can say that boric acid has the potential as an anti-cancer agent in the treatment of lung cancer due to its apoptotic and anti-proliferative effects on A549 cells.
Açıklama
Anahtar Kelimeler
Akciğer Kanseri, Apoptoz, Borik Asit, Lung Cancer, Apoptosis, Boric Acid
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Yirmibes, Seren. (2021). Akciğer kanserinde borik asitin apoptotik etkisinin incelenmesi. İstinye Üniversitesi / Sağlık Bilimleri Enstitüsü / Tıbbi Biyoloji ve Genetik Ana Bilim Dalı. Yüksek Lisans Tezi. İstanbul.
