Adipoz Doku Kaynaklı Ekstrasellüler Veziküllerin Meme Kanseri Hücreleri Üzerine Apoptotik Etkisi

Meme kanseri, en yaygın küresel malignitedir ve kansere bağlı ölümlerin ikinci önde gelen nedenidir. Meme kanserinin erken teşhis edilmesi, farklı tedavi yöntemleri ile tedavi başarı oranını yükseltmektedir. Ancak ilerleyen evrelerde ise hem tedavi başarı oranı düşmektedir hem de güncel tedavi yöntemlerinden kemoterapi veya radyoterapinin uygulanmasının hastaya yan etkileri de olabilmektedir. Bu nedenle kişiye özel, yan etkinin olmadığı tedavi modellerini bulmak gerekir. Eksozomlar doğal nanopartiküller olup, aynı zamanda hücreler arası iletişimde önemli roller oynayan, çok çeşitli lipidler, proteinler, metabolitler, RNA'lar ve DNA'lar içeren küçük hücre dışı veziküller olarak bilinirler. Bu çalışmanın amacı, adipoz doku kaynaklı mezenkimal kök hücrelerden presipitasyon yöntemi ile elde edilen eksozomların (ADEkso) insan meme kanseri hücre hattı, MCF-7, ve meme epitel hücre hattı, MCF10A, üzerinde farklı konsantrasyonlarda Anneksin V/PI metodu kullanılarak apoptotik etkilerinin araştırılmasıdır. Erken apoptotik, geç apoptotik, canlı ve ölü hücreler, her iki hücre hattında 24, 48 ve 72 saat boyunca farklı 40x1010, 20x1010 ve 10x1010 AD-Ekso/mL konsantrasyonları ile muamele edilerek MCF-7 gruplarında toplam yüzde total apoptotik etkileri 24 saat için 40x1010/AD-Ekso/mL’de %58.817±4.2, 48 saat için 0x1010/AD-Ekso/mL 'de %56.37±9 ve 72 saat için 20x1010 AD- Ekso/mL'de %70.9±4.1'dir. AD-Ekso verilen MCF-7 hücre grupları hem kendi aralarında hem de AD-Ekso uygulanmayan MCF-7 hücre grupları ve MCF10A hücre grupları ile karşılaştırıldığında zaman ve doza bağlı olarak aradaki fark istatistiksel olarak anlamlı bulunmuştur (p˂0.05). MCF10A ve MCF-7 kontrol grupları değerlendirilmiş ve anlamlı bir fark gözlenmemiştir (p˃0.05). Sonuç olarak, eksozomlar kanser hücrelerinde apoptozu indükleyerek kanser tedavisinde potansiyel kapasiteye sahip olabilir

Anahtar Kelimeler:

Breast Cancer, Adipose Tissue-Derived Exosomes, Precipitation Method, Apoptosis.

Apoptotic Effect of Adipose Tissue-Derived Extracellular Vesicles on Breast Cancer Cells

Breast cancer is the most common global malignancy and the second leading cause of cancer death. Early diagnosis of breast cancer increases the success rate of treatment with different treatment methods. However, in the advancing stages, both the treatment success rate decreases, and the application of chemotherapy or radiotherapy, which is one of the current treatment methods, may also have side effects on the patient. Therefore, it is necessary to find that personalized treatment models do not have side effects. Exosomes are natural nanoparticles and are also known as small extracellular vesicles which play important roles in intercellular communication, containing a wide variety of lipids, proteins, metabolites, RNAs and DNAs. This study aimed to investigate the apoptotic effects of exosomes obtained from an adipose tissue-derived mesenchymal stem cell (AT-Exo) by precipitation method on human breast cancer MCF-7 and breast epithelial MCF10A at different concentrations by using Annexin V & Dead Cell method. Early apoptotic, late apoptotic, live and dead cells have been evaluated by Annexin V-FITC/PI staining in both cell lines and have found that the percentage of total apoptotic 58.817±4.2%, 56.37±9%, 70.9±4.1% in the 40x1010, 20x1010 ve 10x1010 AT-Exo mL-1 groups for 24h, 48h and 72h respectively. When MCF-7 cell groups given AT-Exo have been compared both among themselves and with MCF-7 and MCF10A cell groups not given AT-Exo, the difference has been statically significant depending on time and dose (p˂0.05). MCF10A and MCF-7 control groups have been evaluated, and no significant difference has been observed (p˃0.05). In conclusion, exosomes may have the potential capacity in cancer therapy by inducing apoptosis in cancer cells.

Keywords:

Breast Cancer, Adipose Tissue-Derived Exosomes, Precipitation Method, Apoptosis.,

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