Mehmet ÇİFTCİ, Deniz ÖZDEMİR, Can Ali AĞCA, Dursun ÖZDEMİR, Kemalcan ŞATANA

İfosfamid ve Kurkumin Kombinasyonun Küçük Hücreli Dışı Akciğer Kanseri Hücresinde Apoptotik Biyobelirteçler ve Hücre Göçü Üzerine Etkileri

Akciğer kanseri, dünyada kansere bağlı en yüksek ölüme neden olan kötü huylu ve saldırgan tümörlerden biridir. İfosfamid, akciğer kanserinin de dâhil olduğu birçok kanser tedavisinde kullanılan alkilleyici bir antineoplastik ajandır. Curcuma longa rizomundan elde edilen bir flavonoid olan kurkumin'in, insan kanserlerinde hücre büyümesinin inhibisyonu, hücre döngüsü dudurulması ve pro-apoptotik etki yoluyla kemoterapötik aktiviteye sahip olduğu gösterilmiştir. Bununla birlikte, İfosfamid ve Kurkumin kombinasyonunun küçük hücreli olmayan akciğer kanseri (NSCLC) üzerindeki etkileri henüz doğrudan ele alınmamıştır. Bu çalışmada akciğer kanseri hücre hattı A549'da, İfosfamid ve Kurkumin kombinasyonunun, hücre proliferasyonu, hücre içi ROS birikimi, apoptozis ve hücre göçü üzerine olan etkileri gerçek-zamanlı hücre analizi, DCFDA floresan işaretleme, western blot ve yara iyileşme-hücre göçü testleri ile araştırılmıştır. A549 hücrelerinde, İfosfamid-kurkumin kombinasyonu ile tedavi sonrasında, hücre içi ROS birikiminde ve pro-apoptotik Bax proteinin düzeyinde bir artış olduğu belirlendi. Ayrıca, kombinasyonun, tedavi edilmeyen ve tek ajan ile tedavi edilen hücrelere kıyasla, anti-apoptotik TIGAR protein düzeyinin azalmasında ve çizilen alana hücre göçünün bastırılmasında etkili olduğu belirlendi. Bulgularımız, Kurkuminin, küçük hücreli olmayan akciğer kanseri hücre hattın A549’da İfosfamidin etkinliğini artırdığını göstermektedir.

Anahtar Kelimeler:

İfosfamid, Kurkumin, A549, Apoptozis, Hücre Göçü

Effects of Ifosfamide and Curcumin Combination on Apoptotic Biomarkers and Cell Migration in Non-Small Cell Lung Cancer Cell

Lung cancer is one of the most common malignancies and aggressive tumour, which causes the highest cancer-related death in the world. Ifosfamide is an alkylating antineoplastic agent used in the treatment of cancer including, lung cancer. Curcumin, a flavonoid from the rhizome of Curcuma longa has been shown to chemotherapeutic activity through inhibition of cell growth, cell cycle arrest, and pro-apoptotic activity in human cancer. However, the effects of Ifosfamide and Curcumin combination on non-small cell lung cancer (NSCLC) remain unclear. In this study, the influences of Ifosfamide, cell proliferation, ROS accumulation, apoptosis, migration, and its combined effects with curcumin were investigated in NSCLC cell line A549 by RT-Cell analyse, DCFDA assay, western blot and wound healing-migration assays. A549 cells were treated with the Ifosfamide-Curcumin combination and the results showed that the combination was effective in ROS accumulation, which contributed to inducing apoptosis via increasing pro-apoptotic Bax and decreasing anti-apoptotic TIGAR, and depression of cell migration. The treatment of combination significantly induced apoptosis, together with the downregulation of TIGAR and upregulation of pro-apoptotic Bax protein. Moreover, Curcumin and Ifosfamide combination suppressed cell migration into the scratched area as compared to untreated cells. Our findings suggest that Curcumin enhanced the efficacy of Ifosfamide in human non-small cell lung cancer cell line.

Keywords:

Ifosfamide, Curcumin, A549, Apoptosis, Cell migration,

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